[Lotus]

Thanks Pegg's, I'll miss yah too.


I've been looking back (sniffles) at some favorite research posts, this one is in the top 5.

Thanks Lotus. Your sage advice is always appreciated.

I am thinking I will try black cohosh liquid extract, although I am not sure it is standardized, on the theory that liquid extract may carry less risk of causing liver damage than capsules. But then again, there may be no real difference in that regard.

I don't see a down-side for red clover, so will probably resume taking that as well.

Hi spanky,

I agree, I have RC as a slight aromatase/progesterone and ERa promoter, as with all NBE use it in moderation.

As mentioned, FSH follicle stimulating hormone stimulates estradiol synthesis, the science is there, so it's possible. Same with vitamin D3, the science is there too, meaning it upreglates T and E2. And as we know, when we try to eliminate most of DHT, what remains?, exactly, T and E2, other hormones too , but for this purpose we'll limit it to the 2 . But let's say we use an anti-androgen in the presence of an aromatase promoter (pick one, WP, forskolin, inositol triphosphate, FSH, etc) which will upregluate both (T and E2) then synthesize thru aromatase. More research (by BN members) should be done on second messengers, (e.g-cAMP,) which imo is key in aroamtase expression and will result in improved breast growth.

Interactions between FSH, estradiol-17 beta and transforming growth factor-beta regulate growth and differentiation in the rat gonad.

Estradiol-17 beta (E2) is a mitogen in vivo for the proliferation of granulosa cells in the rat ovary. E2 is synthesized by the preovulatory follicle through a series of gonadotrophin-dependent events: LH stimulates thecal cells to synthesize androgens (androstenedione and testosterone) which are substrates for FSH-induced aromatization to estrogens in granulosa cells. More recently, we have found that transforming growth factor-beta (TGF-beta) stimulates DNA synthesis in rat granulosa cells in vitro and this effect is augmented by FSH. Since E2 is a mitogen in vivo and TGF-beta is the only known growth factor to stimulate proliferation in vitro, the possible link between the actions of E2 and TGF-beta were examined. E2 stimulated the secretion of a TGF-beta-like factor by rat granulosa cells in culture, and with time DNA synthesis was stimulated. The mitogenic action of E2 was enhanced in the presence of FSH, and attenuated by a neutralizing antibody to TGF-beta. The latter observations have identified TGF-beta as the "missing-link" in the mitogenic actions of E2 on rat granulosa cells. In addition to the growth-promoting actions of TGF-beta plus FSH, TGF-beta enhanced FSH-induced aromatase activity. Consequently, FSH plus TGF-beta stimulates both the proliferation and aromatization capacity of rat granulosa cells. We propose that interactions between FSH, E2 and TGF-beta lead to the exponential increase in serum E2 levels that occurs during the follicular phase of the cycle. Similarly, FSH stimulates the aromatization of exogenous androgens to estrogen by Sertoli cells isolated from immature rat testes, and there is a correlation between FSH-induced aromatization and mitotic activity. We have shown that FSH plus TGF-beta stimulates DNA synthesis in Sertoli cells. Since E2 increases the secretion of TGF-beta by Sertoli cells, interactions between FSH, E2 and TGF-beta may provide the mitogenic stimulus for Sertoli cells during the prepubertal period. In summary, our findings suggest that the estrogen-induced growth of rat granulosa cells is mediated through the production of TGF-beta, which acts as an autocrine regulator of proliferation. We also propose that the growth-promoting actions of FSH on Sertoli cells may depend upon a cascade series of events involving estrogens and TGF-beta.



From post #2618
Sertoli cells synthesize estradiol 17b from testosterone, and when testosterone is introduced with FSH (Follicle-stimulating hormone) it produced a 12 fold increase in E2 synthesis. And is markedly increase when cAMP (Cyclic adenosine monophosphate) is also added. Estrogen also triggers rapid activation of classical second messengers (cAMP, calcium, and inositol triphosphate). On another note, FSH and cAMP produce a 30 fold increase in aromatase, quite possibly making it the strongest aromatase.

Inhibit LH (luteinizing hormone) using black cohosh (nbe) Goserelin (pharma)

Stimulate FSH (follicle stimulating hormone) E2 or red clover, *(essential fatty acids)

Inhibit DHT in the liver. (reishi inhibits serum DHT @ 80%) dutas @93%, finasteride @70% and saw palmetto inhibits DHT @ 32% (combo's possible).

Inhibit adrenal DHT (calmodulin -via the calcium/calmodulin/CaMK pathway) (spiro or licorice root)





* I think future science will confirm that EFA's contribute to FSH synthesis (just my opinion, lol)

And quite possibly from Phospholipids

https://en.m.wikipedia.org/wiki/Phospholipid

[Lotus]

Another favorite (top 5). Understanding this process outlined below can help with incorporating Growth Hormone, Aromatase, using MSM with exercise and intermittent fasting grow new cells. Other information (not listed here,) that's promising is thermogenesis (cold water therapy) that actually produces BAT (brown adipose tissue).

Here's another good NBE hack on MSM for genetic males, intermittent fasting followed by high intensity work outs generates a spike in growth hormones, including IGF-1R, p-IGF-1R, STAT5b, p-STAT5b, and Jak2 in osteoblastic cells and MSCs. MSM benefits muscle & tissue repair.

Researchers at the Intermountain Medical Center Heart Institute found that men who had fasted for 24 hours had a 2000% increase in circulating HGH. Women who were tested had a 1300% increase in HGH. (I'd say that's significant natural growth, as opposed to taking HGH [synthetic]).


MSM enhances GH signaling via the Jak2/STAT5b pathway in osteoblast-like cells and osteoblast differentiation through the activation of STAT5b in MSCs.
Joung YH1, Lim EJ, Darvin P, Chung SC, Jang JW, Do Park K, Lee HK, Kim HS, Park T, Yang YM.
Author information
Abstract
Methylsulfonylmethane (MSM) is a naturally occurring sulfur compound with well-known anti-oxidant properties and anti-inflammatory activities. But, its effects on bone are unknown. Growth hormone (GH) is regulator of bone growth and bone metabolism. GH activates several signaling pathways such as the Janus kinase (Jak)/signal transducers and activators of transcription (STAT) pathway, thereby regulating expression of genes including insulin-like growth factor (IGF)-1. GH exerts effects both directly and via IGF-1, which signals by activating the IGF-1 receptor (IGF-1R). In this study, we investigated the effects of MSM on the GH signaling via the Jak/STAT pathway in osteoblasts and the differentiation of primary bone marrow mesenchymal stem cells (MSCs). MSM was not toxic to osteoblastic cells and MSCs. MSM increased the expression of GH-related proteins including IGF-1R, p-IGF-1R, STAT5b, p-STAT5b, and Jak2 in osteoblastic cells and MSCs. MSM increased IGF-1R and GHR mRNA expression in osteoblastic cells. The expression of MSM-induced IGF-1R and GHR was inhibited by AG490, a Jak2 kinase inhibitor. MSM induced binding of STAT5 to the IGF-1R and increased IGF-1 and IGF-1R promoter activities. Analysis of cell extracts by immunoprecipitation and Western blot showed that MSM enhanced GH-induced activation of Jak2/STAT5b. We found that MSM and GH, separately or in combination, activated GH signaling via the Jak2/STAT5b pathway in UMR-106 cells. Using siRNA analysis, we found that STAT5b plays an essential role in GH signaling activation in C3H10T1/2 cells. Osteogenic marker genes (ALP, ON, OCN, BSP, OSX, and Runx2) were activated by MSM, and siRNA-mediated STAT5b knockdown inhibited MSM-induced expression of osteogenic markers. Furthermore, MSM increased ALP activity and the mineralization of MSCs. Taken together, these results indicated that MSM can promote osteogenic differentiation of MSCs through activation of STAT5b.



Growth hormone pulse-activated STAT5 signalling: a unique regulatory mechanism governing sexual dimorphism of liver gene expression.
Waxman DJ1.
Author information
Abstract
Growth hormone (GH) exerts sexually dimorphic effects on liver gene transcription that are regulated by the temporal pattern of pituitary GH release; this release is intermittent in male rats and nearly continuous in females. Comparisons of liver nuclear protein tyrosine phosphorylation in male and female rats have led to the discovery that the liver transcription factor STAT5b is tyrosine phosphorylated in male but not female rats in response to GH pulses. Intermittent plasma GH pulses trigger a rapid and repeated tyrosine phosphorylation and nuclear translocation of liver STAT5b in intact male rats, while the more continuous pattern of GH exposure down-regulates the STAT5b signalling pathway in female rat liver. The central importance of STAT5b for the physiological effects of GH pulses has been verified using a mouse gene knockout model. STAT5b gene disruption leads to a major loss of multiple sexually differentiated responses associated with the sexually dimorphic pattern of pituitary GH secretion. Male-characteristic body growth rates and male-specific liver gene expression are decreased to wild-type female levels in STAT5b-/- males, while female-predominant liver gene products are increased in males to near female levels. STAT5b is thus a liver-expressed, latent cytoplasmic transcription factor that undergoes repeated tyrosine phosphorylation and nuclear translocation in response to intermittent plasma GH stimulation, and is a key intracellular mediator of the stimulatory effects of GH pulses on male-specific liver gene transcription. Other studies indicate, however, that STAT5a and STAT5b are both required for constitutive expression in female, but not male liver, of certain GH-regulated CYP enzymes. GH activation of both STAT5 proteins, which in turn form distinct homodimeric and heterodimeric DNA-binding complexes, is thus an important determinant of the sex-dependent and gene-specific effects that GH has on the liver.

I think it makes sense to take MSM after a high intensity workout, (biotin too, for its abilty to break down carbs). But because MSM induces binding of STAT5 to the IGF-1R and increases IGF-1 and IGF-1R promotes these activities you'd have to give MSM considerable attention for after workout repair. I like the 12-14 hour intermittent fast, followed by High-intensity Interval Training (HIIT) , that's short bursts of intense work followed by less intense activity or rest.


Growth hormone signaling in human adipose and muscle tissue during "feast and famine"; Amplification of exercise stimulation following fasting compared to glucose administration.

Conclusions: This study demonstrates that fasting and exercise act in tandem to amplify STAT-5b target gene expression (SOCS and CISH) in adipose and muscle tissue in accordance with the "feast and famine hypothesis"; the adipose tissue signaling responses which hitherto have not been scrutinized may play a particular role in promoting FFA mobilization.

http://www.eje-online.org/content/early/...1157.short


Fasting and fitness boost human growth hormone

Intermittent fasting for periods ranging from 12-24 hours along with high intensity exercise has a positive effect on boosting human growth hormone (HGH). HGH is a very important protein-based hormone that is produced by the pituitary gland. HGH enhances the cellular repair processes that allow us to age with grace. HGH regulates metabolism to burn fat, build muscle, and slow down the negative effects of stress.

Researchers at the Intermountain Medical Center Heart Institute found that men who had fasted for 24 hours had a 2000% increase in circulating HGH. Women who were tested had a 1300% increase in HGH.

A 2009 study in the British Journal of Sports Medicine showed that lactic acid accumulation helps to trigger HGH. Lactic acid is only produced in response to intense anaerobic training. Aerobic training is not intense enough to produce the kind of lactate triggering of HGH.

Low-intensity, long duration aerobic training is catabolic in nature. This means that it produces lots of free radicals without promoting significant amounts of repair peptides, enzymes and hormones. The net effect is a wearing down of bodily resources.

High-intensity training also produces free radicals but it triggers an abundance of repair peptides, enzymes and hormones to be released. The net effect of this is healthy tissue repair and favorable effects on body composition and anti-aging qualities.

Learn more: http://www.naturalnews.com/034704_interm...z3cAB6XEkK

Effects of growth hormone on adipose tissue
http://www.ncbi.nlm.nih.gov/pubmed/11086655




IGF-1 (insulin like growth factor) activates the biosynthesis of Aromatase, (the key enzyme in the biosynthesis of oestrogen).

In other words, (this will blow your mind), intermittent fasting followed by HIIT (High-intensity Interval Training) raises HGH (IGF-1) by 2000%, what percentage is going to be aromatase?. Sorry, I don't have the answer yet, I don't think anybody does.

What you eat matters after the HIIT workout, skip the carbs/sugars so the GH has a better chance to convert that fat. Take it a step further and add a high FAT/LOW carb diet and really push it into overdrive. As we know estrogen forms the type of subcutaneous seen in females (meaning that curvy figure), we want that nice toned FAT (curves), otherwise the new fat goes right to your gut, (yes some goes to hips and thighs), but the majority will go to visceral fat, which is very difficult to get rid off. Normal breast tissue cannot develop except in the presence of both progestogen and estrogen. Fibrotic, conical breasts and no areola growth indicate that breasts haven't fully matured, progesterone can help correct this.

(GH activation of both STAT5 proteins, which in turn form distinct homodimeric and heterodimeric DNA-binding complexes, is thus an important determinant of the sex-dependent and gene-specific effects that GH has on the liver).




Don't forget vitamin D and biotin,

vitamin D analogs significantly upregulated E2- and DHT-induced CK response. These analogs upregulated the CK response to selective estrogen receptor modulators (SERMs). An estrogenic response (from vitamin D) is seen in the intestinal tract. Vitamin D also helps with hair growth.


If you could do this 3x a week, (imo) the chances of raising growth hormones is far better (higher) than any suppplement could do. (Amazing stuff). These growth spurts (similar to puberty) could provide the spark for new growth that we so desperately want.

[Lotus]

Sheesh, seriously long post. Btw, Clelia is a scientist.

If you didn't catch this post from the research section I'd like to list here and give it a bit more text. The research posted below shows how I got to this theory (hypothesis) about Fatty Acids being a link to quote "that a third signalling pathway, involving cytoplasmic proteins and rapid membrane-initiated responses, serves largely for mitogenic E2-induced effects. " Most of the research is listed, although there's about a dozen more pages of related info in the NBE Strategies thread, Anti-Androgen thread for that matter too. The bottom line from putting all this together is that staight PM or even Hrt doesn't get it done without some other key links, e.g. EFA's essential fatty acids, certain carrier proteins, common links between 17 beta HSD's, aromatase, estrogen receptors, IGF-1, MAPK, PPP, and many others. But you can believe (or not).......your choice, but when I say it all makes a huge difference, it does, even our scientist Clelia states the existence (see page 142 listed below).

See yeah soon.

Ok, I'm gonna give this a shot at defining why essential fatty acids (EFA's) are important for NBE, any car buffs Lol?.

EFA's are like lubricants for car parts (e.g. molecules, steroids, DNA synthesis etc). They help help carry hormones to receptors, in other words, once they arrive at the cell membranes they (EFA's) make them more bioavailable. Soooo.....using these fat solubles supplements keep us squeaky, get it.



Figure 1: Bioactive lipid synthesis, metabolism and signaling pathways.
http://www.nature.com/nchembio/journal/v...94_F1.html

It is now known that estrogens exert their end-organ effect by activating a complex intracellular mechanism. Tissues which respond to estrogen possess intracytoplasmic proteins (receptors) that preferentially bind specific steroids.

For instance, a cell from the uterus will possess 5000–15,000 estrogen receptors whereas a cell from the spleen will have none. These receptors recognize estrogens by their three dimensional and chemical characteristics and bind it with high affinity (KD =10-10), specificity, and saturability.

NBE Strategies (receptor)
http://www.breastnexus.com/showthread.php?tid=22119&page=14&highlight=Receptors


Genomic and non-genomic effects of estrogens on endothelial cells.
http://www.ncbi.nlm.nih.gov/pubmed/15288766#

Palmitoylation-dependent estrogen receptor alpha membrane localization: regulation by 17beta-estradiol.
http://www.ncbi.nlm.nih.gov/pubmed/15496458

Role of ERbeta palmitoylation in the inhibition of human colon cancer cell proliferation.
http://www.ncbi.nlm.nih.gov/pubmed/17395984

S-palmitoylation modulates estrogen receptor alpha localization and functions.
http://www.ncbi.nlm.nih.gov/pubmed/16274718

Estrogen receptor signalling: bases for drug actions.
http://www.ncbi.nlm.nih.gov/pubmed/16178790

Starting off at page #137 to #147 is some very interesting research (page 142, is IMO one of the best inside the program lotus thread).
http://www.breastnexus.com/showthread.php?tid=17436&page=141

Minireview: The Androgen Receptor in Breast Tissues: Growth Inhibitor, Tumor Suppressor, Oncogene?
http://www.ncbi.nlm.nih.gov/pmc/articles...rt=classic
Credit Clelia for this research article (thanks)

Estrogen receptor signalling: bases for drug actions.

Abstract
Estrogen receptors (ERalpha and ERbeta) mediate the effects of 17beta-estradiol (E2) and account for E2 role on growth, development, and homeostasis maintenance in different tissues and organs. ERalpha and ERbeta function as ligand-dependent transcription factors which directly bind to specific estrogen responsive element (ERE) present into DNA and, in turn, regulate the transcription of E2-sensitive genes. In addition, ERalpha and ERbeta, without direct binding to DNA, regulate transcription indirectly by binding to other transcription factors activating or inactivating the transcription of E2-dependent-ERE-devoid genes. Along with these two E2 mechanisms, it has been recently uncovered that a third signalling pathway, involving cytoplasmic proteins and rapid membrane-initiated responses, serves largely for mitogenic E2-induced effects. The commitment of ERbeta in these rapid E2-induced effects is openly debated. This review will focus and summarize the latest findings regarding the multiple E2 molecular mechanisms and underlines the development of our understanding of anti-cancer drugs acting as ER signalling modulators.

Ok, I'll give it a shot, let's use women's androgens as an example , the major androgen in women is androstenedione, and it takes a pathway to testosterone through the androstenedione pathway to estrogen, with a slight detour (and I mean slight, hard to detect) DHT. The scale tips this pathway towards estrogen, part of what keeps females female. This pathway in males is consider a backdoor pathway, but because DHT is so much stronger it dominates through the standard pathway of testosterone and then enzyme 5 alpha reductase gives it a pass to DHT, unless we intercept it through another enzyme called aromatase, which will then convert to estrogen. But the odds are stacked against us unless preventive actions (anti-androgens) aren't out in place. I like to think of this 3 alpha-hydroxysteroid dehydrogenase" or 3b-Adoil for short, as booby trap (pun) for DHT to find along its pathway (downstream if you will).

In between the androgen pathway sits these booby traps (like light switches), that can block DHT. And so far the only thing I saw to prevent this was cortisteriods, (this action is more complicated I'm afraid too) to prevent this, but I don't think that's the end of the story yet, there's always new research coming out, and by this I mean in the way of cancer treatments, e.g. androgen blockade therapies, new trails etc. just a matter of time before its figured out.......hopefully I'll turn something up soon.

List of Corticosteroid Medications
http://www.livestrong.com/article/27014-...dications/

Here's the techinical version, and I'm sorry if here's where I lose yah.

Four human aldo-keto reductases (AKRs) that belong to the AKR1C subfamily function in vitro as 3-keto-, 17-keto- and 20-ketosteroid reductases or as 3alpha-, 17beta- and 20alpha- hydroxysteroid oxidases to varying degrees. By acting as ketosteroid reductases or hydroxysteroid oxidases these AKRs can either convert potent sex hormones (androgens, estrogens and progestins) into their inactive metabolites or they can form potent hormones by catalyzing the reverse reaction. In this manner they may regulate occupancy and trans-activation of steroid hormone receptors.

From an earlier post,


DHT has an estrogenic action,

The existence of this estrogenic DHT metabolite has raised the possibility that estradiol may not be the major estrogen in males [29]. For instance, in the prostate there is a growing body of evidence that 3β-diol, acting through ERβ, may regulate important physiological events.


Recent data have shown that DHT may be converted into 5α-androstane- 3β-17β-diol (3β-diol) in a virtually irreversible reaction. Once considered inactive, 3β-diol is present in high concentrations in the male and indeed has biological activity. However, 3β-diol does not bind to the androgen receptor (AR), but rather to ERα and ERβ, with higher affinity for ERβ. Based upon these findings, we hypothesized that the modulation of AQP9 by DHT could be indirectly mediated by 3β-diol.

---------------------------

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1615873/


Effects of 3-beta-diol, an androgen metabolite with intrinsic estrogen-like effects,

Abstract

Background: Fluid homeostasis is critical for normal function of the male reproductive tract and aquaporins (AQP) play an important role in maintenance of this water and ion balance. Several AQPs have been identified in the male, but their regulation is not fully comprehended. Hormonal regulation of AQPs appears to be dependent on the steroid in the reproductive tract region. AQP9 displays unique hormonal regulation in the efferent ductules and epididymis, as it is regulated by both estrogen and dihydrotestosterone (DHT) in the efferent ductules, but only by DHT in the initial segment epididymis. Recent data have shown that a metabolite of DHT, 5-alpha- androstane-3-beta-17-beta-diol (3-beta-diol), once considered inactive, is also present in high concentrations in the male and indeed has biological activity. 3-beta-diol does not bind to the androgen receptor, but rather to estrogen receptors ER-alpha and ER-beta, with higher affinity for ER-beta. The existence of this estrogenic DHT metabolite has raised the possibility that estradiol may not be the only estrogen to play a major role in the male reproductive system. Considering that both ER-alpha and ER-beta are highly expressed in efferent ductules, we hypothesized that the DHT regulation of AQP9 could be due to the 3-beta-diol metabolite.

Methods: To test this hypothesis, adult male rats were submitted to surgical castration followed by estradiol, DHT or 3-beta-diol replacement. Changes in AQP9 expression in the efferent ductules were investigated by using immunohistochemistry and Western blotting assay.

Results: Data show that, after castration, AQP9 expression was significantly reduced in the efferent ductules. 3- beta-diol injections restored AQP9 expression, similar to DHT and estradiol. The results were confirmed by Western blotting assay.

Conclusion: This is the first evidence that 3-beta-diol has biological activity in the male reproductive tract and that this androgen metabolite has estrogen-like activity in the efferent ductules, whose major function is the reabsorption of luminal fluids.





a) It has been shown that 3β-diol may have hormonal activity, not acting through the AR, but rather as a ligand for both ERα and ERβ.

b) 3β-diol has higher affinity for ERβ [31], which is abundant in the efferent ductule epithelium [40].

c) In human testis, the 3β-diol concentration is higher than DHT and estradiol [44,45]. It is reasonable to postulate that high concentrations of this metabolite may enter the lumen of efferent ductules.

d) The existence of this estrogenic DHT metabolite has raised the possibility that estradiol may not be the major estrogen in males [29]. For instance, in the prostate there is a growing body of evidence that 3β-diol, acting through ERβ, may regulate important physiological events [26,28,32,46].

Also noteworthy is the fact that 3β-diol stimulates ERβ induced transcriptional activity equal to the cognate ligand estradiol, and the transcriptional selectivity of 3β-diol for ERβ is much greater than its binding selectivity [30,46]

-----------------------------


Concentrations of aromatase and estradiol in the prostate are low, indicating that estradiol may not be the only estrogenic molecule to play a role in the prostate. It is known that DHT can be metabolized to 5alpha-androstane-3beta,17beta-diol (3beta-diol), a hormone that binds to ERbeta but not to AR. The concentration of 3beta-diol in prostate is much higher than that of estradiol. Based on the high concentration of 3beta-diol and since this metabolite is a physiological ERbeta ligand, we hypothesized that 3beta-diol would be involved in the regulation of ERbeta expression.





An endocrine pathway in the prostate, ERbeta, AR, 5alpha-androstane-3beta,17beta-diol, and CYP7B1, regulates prostate growth.
http://www.ncbi.nlm.nih.gov/pubmed/12370428

I've spent more time researching on this backdoor estrogenic action of DHT, aka estrogen receptor beta. From what I see when DHT is metabolized in the liver we can force it to this ER-b back door, thereby lessening (or inactivating) it's potential. And imo cortisteriods inactivates DHT.

Hmmmm so is reishi still good to take? i guess taking everything in moderation is always better but NBE is such a long journey thus everything will be kind of long term type

I forget to include these studies, although somewhat technical it's still some solid info on reishi:


Ganoderma lucidum: A Potent Pharmacological Macrofungus
http://www.researchgate.net/profile/Prakash_Bisen/publication/40032434_Ganoderma_lucidum_a_potent_pharmacological_macrofungus/links/0fcfd505b4749c887f000000.pdf?ev=pub_ext_doc_dl&origin=publication_detail&inViewer=true


Ganoderma – A therapeutic fungal biofactory
http://www.researchgate.net/profile/Russell_Paterson/publication/6882609_Ganoderma_-_a_therapeutic_fungal_biofactory/links/00b7d5225ef366b7c6000000.pdf?ev=pub_ext_doc_dl&origin=publication_detail&inViewer=true


Target proteins of ganoderic acid DM provides clues to various pharmacological mechanisms:
http://www.nature.com/srep/2012/121130/s...p00905.pdf

______________________________

Other info:

Effect of epidermal growth factor and prostaglandin on the expression of aromatase (CYP19) in human adrenocortical carcinoma cell line NCI-H295R cells
http://joe.endocrinology-journals.org/co...9.full.pdf

Comparative effects of DHEA vs. testosterone, dihydrotestosterone, and estradiol on proliferation and gene expression in human LNCaP prostate cancer cells
http://ajpendo.physiology.org/content/aj...3.full.pdf

Nutritional Influences on Estrogen Metabolism
http://www.afmcp-sa.com/ansr/MET451%20En...20ANSR.pdf

yep, maybe in men the estrogenic activity of soy is more effective than in women, but also it depends on individual genetics. You'll see in the link below, a very good article that summarize a lot of papers about phytoestrogens. After reading that, you can just say: yes, it could wbe helpful as it could be harmful... and maybe it's wise stay in the middle, not exceed:
http://foodforbreastcancer.com/foods/gen...d-daidzein

an extract of the article: (here it is something in english about equol and its conversion

Equol has been shown to have the strongest binding affinities and estrogenic activities (especially for ERβ) among the daidzin metabolites and has been hypothesized to be largely responsible for the estrogen-like activities of soy and its isoflavones. However, there is a great deal of variation among individuals in the metabolism of genistin and daidzin, which appears to be dependent partly on environmental factors, including other components of the diet, and partly on genetic factors.

Only 25% to 35% of the U.S. Caucasian population is capable of converting daidzein to equol, whereas people in high soy consumption areas of Asia have rates closer to 40% to 60%. There is some evidence that Hispanic or Latino women are also more likely to be equol producers. Approximately 80% to 90% of people harbor the bacteria required to produce ODMA. The frequency of equol producers in one study of vegetarians was found to be 59%, similar to the reported frequency in Japanese adults consuming soy, and much higher than for nonvegetarian adults (25%). One Japanese study found that consumption of dairy products was significantly higher in those who did not excrete equol than in those who did.



other papers that i looked at today:

http://www.ncbi.nlm.nih.gov/pubmed/25789108

http://www.ncbi.nlm.nih.gov/pubmed/25673549

http://www.ncbi.nlm.nih.gov/pubmed/25338271

http://www.ncbi.nlm.nih.gov/pubmed/25302172

http://www.ncbi.nlm.nih.gov/pubmed/25263312

http://www.ncbi.nlm.nih.gov/pubmed/25236805

isoflavones in the brain: http://www.ncbi.nlm.nih.gov/pubmed/25232349

http://www.ncbi.nlm.nih.gov/pubmed/22510793

http://www.ncbi.nlm.nih.gov/pubmed/25592466

http://www.ncbi.nlm.nih.gov/pubmed/24504368

http://www.ncbi.nlm.nih.gov/pubmed/24531783

http://www.ncbi.nlm.nih.gov/pubmed/24053483

Oh yeah ......you know I'll want to talk about this research studies , their just screaming "hey I'm here, read me" ......solve me......

Structure, function and tissue-specific gene expression of 3β-hydroxysteroid dehydrogenase/5-ene-4-ene isomerase enzymes in classical and peripheral intracrine steroidogenic tissues.
________________________________________
data indicate that the presence of multiple 3β-HSD isoenzymes offers the possibility of tissue-specific expression and regulation of this enzymatic activity that plays an essential role in the biosynthesis of all hormonal steroids in classical as well as peripheral intracrine steroidogenic tissues.

http://www.ncbi.nlm.nih.gov/pubmed/22217825

Bovine adrenal 3beta-hydroxysteroid dehydrogenase (E.C. 1.1.1. 145)/5-ene-4-ene isomerase (E.C. 5.3.3.1): characterization and its inhibition by isoflavones.
____________________________________________
The isoflavones daidzein, genistein, biochanin A and formononetin inhibit potently and preferentially the gamma-isozymes of mammalian alcohol dehydrogenase (gammagamma-ADH), the only ADH isozyme that catalyzes the oxidation of 3beta-hydroxysteroids. Based on these results, we proposed that these isoflavones might also act on other enzymes involved in 3beta-hydroxysteroid metabolism. Recently, we showed that they indeed are potent inhibitors of a bacterial beta-hydroxysteroid dehydrogenase (beta-HSD). To extend this finding to the mammalian systems, we hereby purified, characterized and studied the effects of isoflavones and structurally related compounds on, a bovine adrenal 3beta-hydroxysteroid dehydrogenase (3beta-HSD). This enzyme catalyzes the oxidation of 3beta-hydroxysteroids but not 3alpha-, 11beta- or 17beta-hydroxysteroids. The same enzyme also catalyzes 5-ene-4-ene isomerization, converting 5-pregnen 3, 20-dione to progesterone. The K(m) values of its dehydrogenase activity determined for a list of 3beta-hydroxysteroid substrates are similar (1 to 2 microM) and that of its isomerase activity, determined with 5-pregnen 3, 20-dione as a substrate, is 10 microM. The k(cat) value determined for its isomerase activity (18.2 min(-1)) is also higher than that for its dehydrogenase activity (1.4-2.4 min(-1)). A survey of more than 30 isoflavones and structurally related compounds revealed that daidzein, genistein, biochanin A and formononetin inhibit both the dehydrogenase and isomerase activity of this enzyme. Inhibition is potent and concentration dependent. IC(50) values determined for these compounds range from 0.4 to 11 microM, within the plasma and urine concentration ranges of daidzein and genistein of individuals on vegetarian diet or semi-vegetarian diet. These results suggest that dietary isoflavones may exert their biological effects by inhibiting the action of 3beta-HSD, a key enzyme of neurosteroid and/or steroid hormone biosynthesis.
http://www.ncbi.nlm.nih.gov/pubmed/10704908

estrogenic isoflavones are potent inhibitors of beta-hydroxysteroid dehydrogenase of P. testosteronii.
___________________________________________
The isoflavones daidzein, genistein, biochanin A and formononetin selectively inhibit the gamma-isozymes of mammalian alcohol dehydrogenase (ADH). Since gamma-ADH is the only ADH isoform that catalyzes 3 beta-hydroxysteroid oxidation, it was conjectured that these isoflavones might also inhibit other enzymes involved in 3 beta-hydroxysteroid metabolism. P. testosteronii beta-hydroxysteroid dehydrogenase (beta-HSD) was used to evaluate this hypothesis. Indeed, all isoflavones that inhibit gamma-ADH were found to be potent inhibitors of beta-HSD. Both the 3 beta- and 17 beta-HSD activities of the enzyme are inhibited. Kinetic analyses with pregnenolone (3-beta-OH) and testosterone (17-beta-OH) as substrates reveal that daidzein and genistein inhibit beta-HSD competitively with respect to the sterol substrates. Their Ki values are very similar and range from 0.013 to 0.02 microM. These results suggest that isoflavones may exert some of their biological effects by modulating activities of enzymes that metabolize steroids critical to hormonal and/or neuronal functions.
http://www.ncbi.nlm.nih.gov/pubmed/7488041#

What i do not understand up there underlined is:
why addiction of DHT didn't decrease gland morphology in adult mammary gland?
why affected just the midpuberty, retarding development?
maybe in the adult mammary gland, DHT in extra amount, is it converted in 3-diol? so it can neutralize is own androgenic effect? I don't know...maybe it's that back-door effect, but result is not estrogenic, otherwise mammary gland should have developed..

I could understand just flutamide action... in midpuberty should work less because of less presence of AR receptor. When AR receptors increase in post-puberty, the antagonism of them promote growing.

If we low DHT, we should mimic a bit flutamide action. And also, more testosterone will be converted in estradiol, as mentioned in your sign

Hi Clelia,

Hope you had a good weekend,

Sorry I jumped ahead a few spots, getting back to your question. 3b-diol does explain the back door response. I'm just wondering if there's a re-absorption response before being excreted?, (e.g. re-activate DHT, one more time) as seen with estrogen metabolites. I dunno?,

But in males it does seem that 3-diol has estrogen action (ER-b) in epithelia of efferent ductules and the epididymis. I'm going to post about 4-5 posts regarding this process (male ER-b) that I posted a few months ago if that's ok. If rather focus on mammary DHT's fine too, either way, there's much to solve with your help.

So what if there was way to influence an estrogen action in the Leydig cells since they already include estrogen receptors. Well, a pathway needs to be established. Here is one possible source, or could be a possible action.

Sperm, a source of estrogen
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1518866/
Environ Health Perspect. Oct 1995; 103(Suppl 7): 59–62.
PMCID: PMC1518866
Research Article
Sperm, a source of estrogen.

Other info: it's being researched already.

Estrogen signaling in testicular cells.

Aromatase transforms irreversibly androgens into estrogens and is present in the endoplasmic reticulum of various tissues including the mammalian testis. In rat all testicular cells except peritubular cells express aromatase. Indeed in adult rat germ cells (pachytene spermatocytes and round spermatids) we have demonstrated the presence of a functional aromatase (transcript, protein and biological activity) and the estrogen output is equivalent to that of Leydig cells. In addition in the adult rat, transcripts of aromatase vary according to the germ cell type and to the stages of seminiferous epithelium. By contrast with the androgen receptors mainly localized in somatic cells, estrogen receptors (ERs) are described in most of the testicular cells including germ cells. Moreover, besides the presence of high affinity ERα and/or ERβ, a rapid membrane effect has been recently reported and we demonstrated that GPR30 (a transmembrane intracellular estrogen receptor) is expressed in adult rat pachytene spermatocytes. Therefore estrogens through both GPR30 and ERα are able to activate the rapid EGFR/ERK/c-jun signaling cascade, which in turn triggers an apoptotic mitochondrial pathway involving an increase in Bax expression and a concomitant reduction of cyclin A1 and B1 gene levels. In another study in round spermatids of adult rat we have shown that the rapid membrane effect of estradiol is also efficient in controlling apoptosis and maturation / differentiation of these haploid germ cells. In man the presence of a biologically active aromatase and of estrogen receptors has been reported in Leydig cells, but also in immature germ cells and ejaculated spermatozoa. Thus the role of estrogen (intracrine, autocrine and / or paracrine) in spermatogenesis (proliferation, apoptosis, survival and maturation) and more generally, in male reproduction is now evidenced taking into account the simultaneous presence of a biologically active aromatase and the widespread distribution of estrogen receptors especially in haploid germ cells.

oK then I just have to ask...
Would men's sperm be a significant source of aromatase?

I think so, the study concluded that Leydig cells, germ cells, and seminiferous tubules all showed positive stains for aromatase. But it has to do more with the head (tip) of sperm.

I take that back, it's the tail that has the most aromatase and the head of the epididymis displays estrogen receptors where estrogen synthesis occurs.

Summary diagram of potential estrogen action in epithelia of efferent ductules and the epididymis. At least 4 potential pathways are considered. 1) testosterone (T) can enter the cell or be converted to E2 by aromatase (Arom) found in luminal sperm [54]. Testosterone binds AR and translocates into the nucleus, where it binds to AREs, on the promoter regions of genes with or without EREs. 2) E2 will either enter the cell, as did testosterone or bind the membrane ESR (mESR1). It remains controversial whether E2 binds GPR30 in the membrane [144] or collaborates with mESR1 to mediate epidermal growth factor receptor (EGFR) activation (nonclassical) of kinases and phosphorylation [180]. It is well known that E2 binds ESR1 and translocates into the nucleus for classical mediation of transcription through EREs and recruitment of numerous cofactor proteins (C1–3). It is unknown how AR and ESR1 compete for these cofactors, or what happens when the steroid balance is altered in a cell expressing both receptors. 3) The ESR1 can also be activated through phosphorylation and mediate transcription through the ERE. 4) It is well documented in other tissues that mESR1 binds E2, resulting in very rapid cell signaling [84, 175, 178]. This rapid steroid activity through the membrane receptor involves caveolin-1, G proteins, and the phosphorylation/dephosphorylation cascades, which mediate transcription either through the ESR1/ERE or other transcription factors (TF).
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3071263/


I think we made an important step in solving the Estrogen action in Genetic Males and NBE.

Or a 67 yard field goal.

Clelia,
The part of the re-absorption might come from Aldo-keto reductases (AKRs), what do you think?.
Example:

Type 3 3alpha-hydroxysteroid dehydrogenase (aldo-keto reductase 1C2, aka-AKR acts solely as a reductase to convert 5alpha-dihydrotestosterone (DHT), a potent ligand for the AR

_____________________________________________

It's like deconstructing a model (call it a airplane model) that someone else built, only you're working in reverse to deconstruct right. Same applies here, you see a study that states 5 alpha reductase is reduced in the liver, now maybe this study was for cancer research or something similar. Let's take one of these studies,

Role of human type 3 3alpha-hydroxysteroid dehydrogenase (AKR1C2) in androgen metabolism of prostate cancer cells.

Aldo-keto reductases (AKRs) is another superfamily class of enzymes like the Cytochrome P450 enzyme super family, which are present in most tissues of the body, and play important roles in hormone synthesis and breakdown (including estrogen and testosterone synthesis and metabolism), cholesterol synthesis, and vitamin D metabolism. Cytochrome P450 enzymes also function to metabolize potentially toxic compounds, including drugs and products of endogenous metabolism such as bilirubin, principally in the liver.

AKRs are involved in the development and progression of many cancers, as well as chemotherapeutic drug resistance. AKR1B1 and AKR1B10 are overexpressed in tumors, such as liver, breast, and lung cancer. Several AKRs (AKR1A1, AKR1B10, and AKR1C1-3) are involved in tobacco-carcinogenesis, but they also catalyze the detoxication of nicotine derived nitrosamino ketones. In addition, AKR1C1-3 enzymes play a key role in the regulation of proliferative signaling in hormone dependent cancers.

So what they did in this study was to cut off the androgen synthesis to the receptors using another steroid , Four human aldo-keto reductases (AKRs) that belong to the AKR1C subfamily function in vitro as 3-keto-, 17-keto- and 20-ketosteroid reductases or as 3alpha-, 17beta- and 20alpha- hydroxysteroid oxidases to varying degrees. By acting as ketosteroid reductases or hydroxysteroid oxidases these AKRs can either convert potent sex hormones (androgens, estrogens and progestins) into their inactive metabolites or they can form potent hormones by catalyzing the reverse reaction. In this manner they may regulate occupancy and trans-activation of steroid hormone receptors.

In English, I want to find the link to activate AKR1c in the liver to shut off the androgen receptors therefore DHT never gets activated, simple right?.

Regulates access of 5alpha-DHT to the androgen receptor.

Abstract
Pairs of hydroxysteroid dehydrogenases (HSDs) govern ligand access to steroid receptors in target tissues and act as molecular switches. By acting as reductases or oxidases, HSDs convert potent ligands into their cognate inactive metabolites or vice versa. This pre-receptor regulation of steroid hormone action may have profound effects on hormonal response. We have identified the HSDs responsible for regulating ligand access to the androgen receptor (AR) in human prostate. Type 3 3alpha-hydroxysteroid dehydrogenase (aldo-keto reductase 1C2, aka-AKR acts solely as a reductase to convert 5alpha-dihydrotestosterone (DHT), a potent ligand for the AR (K(d)=10(-11)M for the AR), to the inactive androgen 3alpha-androstanediol (K(d)=10(-6)M for the AR); while RoDH like 3alpha-HSD (a short-chain dehydrogenase/reductase (SDR)) acts solely as an oxidase to convert 3alpha-androstanediol back to 5alpha-DHT. Our studies suggest that aldo-keto reductase (AKRs) and SDRs function as reductases and oxidases, respectively, to control ligand access to nuclear receptors.
http://www.ncbi.nlm.nih.gov/pubmed/17223255

Notice how Aldo-keto reductases (AKRs) position themselves between DHT and 3-diols, this is where the estrogenic action takes place. These actions of AKR1C's takes place in androgen metabolism of the prostate.

Aldo-keto reductases (AKRs) is another superfamily class of enzymes like the Cytochrome P450 enzyme super family.






Estrogen receptor β and 17β-hydroxysteroid dehydrogenase type 6, a growth regulatory pathway that is lost in prostate cancer

Estrogen receptor β (ERβ) is activated in the prostate by 5α-andros- tane-3β,17β-diol (3β-Adiol) where it exerts antiproliferative activity. The proliferative action of the androgen receptor is activated by 5α- dihydrotestosterone (DHT). Thus, prostate growth is governed by the balance between androgen receptor and ERβ activation. 3β- Adiol is a high-affinity ligand and agonist of ERβ and is derived from DHT by 3-keto reductase/3β-hydroxysteroid dehydrogenase en- zymes. Here, we demonstrate that, when it is expressed in living cells containing an estrogen response element-luciferase reporter, 17β-hydroxysteroid dehydrogenase type 6 (17βHSD6) converts the androgen DHT to the estrogen 3β-Adiol, and this leads to activation of the ERβ reporter. This conversion of DHT occurs at concentrations that are in the physiological range of this hormone in the prostate. Immunohistochemical analysis revealed that 17βHSD6 is expressed in ERβ-positive epithelial cells of the human prostate and that, in prostate cancers of Gleason grade higher than 3, both ERβ and 17βHSD6 are undetectable. Both proteins were present in benign prostatic hyperplasia samples. These observations reveal that for- mation of 3β-Adiol via 17βHSD6 from DHT is an important growth regulatory pathway that is lost in prostate cancer.

http://www.ncbi.nlm.nih.gov/pmc/articles...117772.pdf

_________________________________________________

As you can see the pathway for Testosterone, Approximately 7% of testosterone is reduced to 5α-dihydrotestosterone (DHT) by the cytochrome P450 enzyme 5α-reductase, an enzyme highly expressed in male sex organs and hair follicles. Approximately 0.3% of testosterone is converted into estradiol by aromatase (CYP19A1) an enzyme expressed in the brain, liver, and adipose tissues. Note-the percentages are slightly off, (multiple sources).

By inhibiting the enzyme 5-alpha reductase and promoting the enzyme aromatase along with your choice phytoestrogens or pharma E is key for breast growth in bio-males.

Herbs that convert aromatase-White Peony, Liorice root, Genistein (PM), BO.

Herbs that help block 5 ar, Licorice root, WP, Reishi, SP, pygeum, nettle root (NR is tricky though), BO (not an herb), chinese skullcap, linolenic acid, green tea, progesterone cream is a strong 5 ar, pumpkin seed oil, linolenic acid.

(Pharma-Dutasteride and Finasteride). Both finasteride and dutasteride undergo extensive hepatic metabolism primarily via the cytochrome P450 3A4 (CYP 3A4) isoenzyme system.

Bruno deLignieres, an impeccable French researcher and Thiery Hertoghe, MD, fourth generation in the most distinguished family of endocrinologists in Belgium, have put forth the notion that rising estrogen levels are more likely to be the initiator of the process and that testosterone and DHT may then be a secondary player (promoter). In fact, phytotherapy (large doses of phytoestrogens - soy) is commonly used in European medical practices to treat BPH.

(Jonathan Wright and Eugene Shippen have written excellent, and popular books, discussing these more far-sighted notions all too commonly overlooked and even rejected in current conventional American Medical thinking.)

Testosterone is reduced by the enzyme 5-a-reductase to DHT which is then thought to be the real culprit. The argument between the use of Saw Palmetto, Pygeum and Pumpkin seeds vs Proscar are both directed at blocking this enzyme. Strangely, DHT is most important for sexual vigor, so blocking this step may have some unintended consequences!

On the other hand, Testosterone is also converted into estradiol by aromatase (producing the aromatic ring). This occurs increasingly with age in the liver but most importantly ... in the fat stores.

http://www.antiaging.com/andropause/andropause2.html

Its been stated here before that the Androgen to Estrogen pathway is easier than the Testosterone to Estrogen pathway, and once again aromatase continues to demonstrate the factual evidence.

A couple of French researchers recently reported this:

Testosterone is reduced by the enzyme 5-a-reductase to DHT which is then thought to be the real culprit. The argument between the use of Saw Palmetto, Pygeum and Pumpkin seeds vs Proscar are both directed at blocking this enzyme. Strangely, DHT is most important for sexual vigor, so blocking this step may have some unintended consequences!

On the other hand, Testosterone is also converted into estradiol by aromatase (producing the aromatic ring). This occurs increasingly with age in the liver but most importantly ... in the fat stores.
Now you see the connection. As we age, and frequently gain increasing fat stores, we are feeding the aromatase connection, increasing our estradiol levels and if this theory holds, increasing the promotion of prostate disease.

Also that rising estrogen levels are more likely to be the initiator of the process and that testosterone and DHT may then be a secondary player (promoter). In fact, phytotherapy (large doses of phytoestrogens - soy) is commonly used in European medical practices to treat BPH.

Another example of the androgen/estrogen pathway:



http://www.antiaging.com/andropause/andropause2.html

[/quote]

That's a good find, Clelia. Thanks!

happy you appreciate, you're welcome

what's your opinion?, sorry.... I've listed like 10 issues lol.

yep, lot of stuff to read here ... i'm reading everything you reported.
I will answer later on.

The first thing that I want to say is...
I spent an afternoon trying to understand this:

In this study, we investigated whether development of the murine mammary gland could be altered by stimulating or suppressing androgen receptor (AR) signaling in vivo. Intact virgin female mice aged 5 wk (midpuberty) or 12 wk (postpuberty) were implanted with slow-release pellets containing either placebo, 5α-dihydrotestosterone (1.5 mg) or the AR antagonist flutamide (60 mg). Treatment with 5α-dihydrotestosterone from midpuberty to 12 wk of age-retarded ductal extension by 40% (P = 0.007), but treatment from 12-21 wk had no significant effect on gland morphology. In contrast, inhibition of AR signaling with flutamide from midpuberty had no effect on the mammary gland, but flutamide treatment from 12-21 wk increased ductal branching (P = 0.004) and proliferation (P = 0.03) of breast epithelial cells. The increased proliferation in flutamide-treated mice was not correlated with serum estradiol levels or estrogen receptor-α (ERα) expression.

http://www.ncbi.nlm.nih.gov/pubmed/21846805

moreover: In control mice, the frequency and intensity of AR immunostaining in mammary epithelial cells was significantly increased in the 12- to 21-wk treatment group compared with the 5- to 12-wk group (P < 0.001). In contrast, no change in ERα occurred, resulting in a marked increase in the AR to ERα ratio from 0.56 (±0.12) to 1.47 (±0.10).
--> this means that receptor ERalfa is in the same quantity, in midpuberty and postpuberty. In contrast, AR receptor triple from middlepuberty to post-puberty, and that's why breast stop to grow in female (because AR receptors increase a lot).

Also we see from your favourite article that male rats depleted of AR receptors, develop full mammary gland.

So we see how important is AR signals in breast size (despite everything else).

What i do not understand up there underlined is:
why addiction of DHT didn't decrease gland morphology in adult mammary gland?
why affected just the midpuberty, retarding development?
maybe in the adult mammary gland, DHT in extra amount, is it converted in 3-diol? so it can neutralize is own androgenic effect? I don't know...maybe it's that back-door effect, but result is not estrogenic, otherwise mammary gland should have developed..

I could understand just flutamide action... in midpuberty should work less because of less presence of AR receptor. When AR receptors increase in post-puberty, the antagonism of them promote growing.

If we low DHT, we should mimic a bit flutamide action. And also, more testosterone will be converted in estradiol, as mentioned in your sign

Circulating 2-hydroxy and 16-α hydroxy estrone levels and risk of breast cancer among postmenopausal women

Thank you about this information, i read the abstract but i didn't get it... it talks about a ratio between two components, but i don't see what ratio. I will open the pdf... but not now... (no time left), btw, do you know if there is something that low this risk?

On another note....I've seen that EPA and DHA reduces the risk of breast cancer by as much as a 32% reduction, I don't know the dosage.

the article you posted says:
"The purpose of the WHEL Study was to assess whether a major increase in vegetable, fruit, and fiber intake and a decrease in dietary fat intake reduces the risk of recurrent and new primary breast cancer and all-cause mortality among women with previously treated early-stage breast cancer.
Women with higher intakes of EPA and DHA from food had an approximate 25% reduced risk of additional breast cancer events, compared with the lowest tertile of intake. Women with higher intakes of EPA and DHA from food had a dose-dependent reduced risk of all-cause mortality. EPA and DHA intake from fish oil supplements was not associated with breast cancer outcomes. The investigation indicates that marine fatty acids from food are associated with reduced risk of additional breast cancer events and all-cause mortality. J. Nutr. 141: 201–206, 2011."
maybe you can find the answer at your question in this table:

" Anti-androgenic activity of fatty acids." http://www.ncbi.nlm.nih.gov/pubmed/19353546 (2009)

Great link, thank you so much, I can only think of two supplements that cam meet that demand........coconut oil and EPO-evening primrose oil.

and hemp seed oil

I've got to go now. I know that i still miss something, i'll come back next week, i'm off for the weekend. see you!

Hi Lotus, i like reading your posts, now I have no much time to answer, but I can tell you something

Thanks Clelia, , I appreciate your time.

Research is often controversial, because maybe in different studies there are differences that could affect results (for example, in vivo and in vitro can change final results).

Great point, I noticed limitations in some studies (e.g. available test samples w/regards to country's ban or limitations) could affect results, but I understand what you mean.

Also, we should take account of the target of the subject: different tissues can respond in different ways, with same inizial conditions. This is due to the variability of the receptor expressed in every tissue, which often are not the same and in same amount (understandably).

Ok, Like multiple response, or unintended consequence.

So, your research about the "estrogen DHT metabolite", is based on prostate, not breast tissue or skin. That's why men become bald: there is androgen dominance in their skin, and fighting DHT is proved good to grow hair.
Also, the DHT metabolite, interacts with ERb, and we know that alfa is better for breast growth, isnt it?

BPH/prostate research does seemed skewed towards 5-ar inhibitors/ anti DHT. Since the prostate is pro ER-a it seems likely estrogen could be a mediator of cancers too.

Its good to try to convert DHT in estrogen metabolite, but i think its better to shut it down, at least for breast growth.

I've seen some promising research that includes androgen blockade therapy, 17beta -HSD, even using prolactin molecules to box out DHT because of their larger size, suggesting to me PRL is DHT inhibitor. But I think COX is also an aromatase at PGE.

And if you do this, what about your prostate risk? Since the metabolite help prevent prostate cancer, what if you low it? I think you should read this also, maybe there are other mechanisms involved, in prostate cancer:

Yes, elimaniting androgen/DHT ip even in Mtf has long term consequence. The biological affects of androgens are are still needed. The assumptation of testosterone being poison is often misinterpreted. Testosterone is the sex hormone that converts to all estrogens, without T Mtf wouldn't make the necessary conversion to transition. I think it's a mistake to reduce testosterone, the reduction is needed at DHT...... and the reason is quite obvious.

" Anti-androgenic activity of fatty acids." www.ncbi.nlm.nih.gov/pubmed/19353546 (2009)

Great link, thank you so much, I can only think of two supplements that cam meet that demand........coconut oil and EPO-evening primrose oil.

The question we should be asking is how much......

As in how much Testosterone (DHT) do I need to overcome daily, or how much estradiol besides my .3 mg I produce daily is needed.

Here's what I mean--

According to the National Institutes of Health, the normal range of testosterone is 30 to 95 nanograms per deciliter (ng/dL) for women and 300 to 1,200 ng/dL for men, but individual laboratories might have a slightly different range that they consider normal. Also keep in mind that the levels vary with age. In women, the level of testosterone in the blood is lowest during puberty and adolescence, and is highest in pre- and post-menopausal women. For men, the levels increase during puberty and stay steady for much of their young adult life. They then slowly begin to decline during middle and older age.
http://www.livestrong.com/article/239396...r-a-woman/


Men and women produce exactly the same hormones, but in different amounts: as a rule, men produce 20 times more testosterone than women, while women produce more estrogen and progesterone. As with most things in nature, this "norm" can become imbalanced, and some women may have higher levels of testosterone, causing a unique set of symptoms.

Daily averages-

Endogenous avg. produced daily (males)

MEN
-Hormone ( FSH): 2 - 18 mIU/ml
-Testosterone 3mg to 10mg (daily)
-Prolactin 7 - 18 ng/ml
-FT-Free T is about 2% (this is the functional T)
-BT-Bound T or 98%
-Albumin 38% (bloodstream)
-SHBG is 60% (sex-hormone-binding-globulin)
-DHT approximately 7% of T is reduced by 5 ar
-Estradiol approximately 0.3% of testosterone is converted into E2 by aromatase (CYP19A1) of that 0.3%, 20% is directly produced by the testes. Roughly 60% of circulating estradiol is derived from direct testicular secretion or from conversion of testicular androgens. The remaining fraction is derived from peripheral conversion of adrenal androgens. The serum levels of estradiol in males (14 - 55 pg/mL) are roughly comparable to those of postmenopausal women (< 35 pg/mL).

Endogenous avg. produced daily (females)

WOMEN
-Testosterone 0.05 mg (produced daily)
-FT-Free T normal calculated free testosterone is 0.4 – 0.8 ng/dl (or 40 – 80 pg/dl).
-Albumin 34% bloodstream)
-SHBG is 66% (sex-hormone-binding-globulin)
-Estradiol 70 to 500 mg of estradiol daily, (depending on the phase of the menstrual cycle. This is converted primarily to estrone, which circulates in roughly equal proportion to estradiol, and to small amounts of estriol.)
-Estradiol in postmenopausal women (< 35 pg/mL).
-Progesterone levels tend to be < 2 ng/ml prior to ovulation, and > 5 ng/ml after ovulation. If pregnancy occurs, human chorionic gonadotropin is released maintaining the corpus leuteum allowing it to maintain levels of progesterone.

Avg tests

Hormone Follicular Day of LH Surge Mid-luteal
-Follicle Stimulating (FSH) < 10 mIU/ml > 15 mIU/ml -
-Luteinizing Hormone-(LH) < 7 mIU/ml > 15 mIU/ml -
-Prolactin < 25 ng/ml
-Thyroid Stimulating Hormone 0.4 - 3.8 uIU/ml (TSH)
-Estradiol ( E2) < 50 pg/ml ( Day 3) > 100 pg/ml
-Progesterone < 1.5 ng/ml > 15 ng/ml




Reference Values
Free Estradiol, Percent
Reference Ranges (%)

Adult Males 1.7 - 5.4
Adult Females 1.6 - 3.6

Free Estradiol, Serum
Reference Ranges (pg/mL)

Adult Males 0.2 - 1.5
Adult Females 0.6 - 7.1

Sex Hormone Binding Globulin (SHBG), Serum
Reference Ranges
Adult Males 20 - 60
Adult Female
Premenopausal 40 - 120
Postmenopausal 28 - 112

the most complete list here:
http://wikipedia.org/wiki/Reference_rang...lood_tests

This is very interesting:

Normal Hormone Proportions
http://georgiahormones.com/pdf/Brochure_...rtions.pdf

[Lotus]

Sheesh, seriously long post. Btw, Clelia is a scientist.

If you didn't catch this post from the research section I'd like to list here and give it a bit more text. The research posted below shows how I got to this theory (hypothesis) about Fatty Acids being a link to quote "that a third signalling pathway, involving cytoplasmic proteins and rapid membrane-initiated responses, serves largely for mitogenic E2-induced effects. " Most of the research is listed, although there's about a dozen more pages of related info in the NBE Strategies thread, Anti-Androgen thread for that matter too. The bottom line from putting all this together is that staight PM or even Hrt doesn't get it done without some other key links, e.g. EFA's essential fatty acids, certain carrier proteins, common links between 17 beta HSD's, aromatase, estrogen receptors, IGF-1, MAPK, PPP, and many others. But you can believe (or not).......your choice, but when I say it all makes a huge difference, it does, even our scientist Clelia states the existence (see page 142 listed below).

See yeah soon.

Ok, I'm gonna give this a shot at defining why essential fatty acids (EFA's) are important for NBE, any car buffs Lol?.

EFA's are like lubricants for car parts (e.g. molecules, steroids, DNA synthesis etc). They help help carry hormones to receptors, in other words, once they arrive at the cell membranes they (EFA's) make them more bioavailable. Soooo.....using these fat solubles supplements keep us squeaky, get it.



Figure 1: Bioactive lipid synthesis, metabolism and signaling pathways.
http://www.nature.com/nchembio/journal/v...94_F1.html

It is now known that estrogens exert their end-organ effect by activating a complex intracellular mechanism. Tissues which respond to estrogen possess intracytoplasmic proteins (receptors) that preferentially bind specific steroids.

For instance, a cell from the uterus will possess 5000–15,000 estrogen receptors whereas a cell from the spleen will have none. These receptors recognize estrogens by their three dimensional and chemical characteristics and bind it with high affinity (KD =10-10), specificity, and saturability.

NBE Strategies (receptor)
http://www.breastnexus.com/showthread.php?tid=22119&page=14&highlight=Receptors


Genomic and non-genomic effects of estrogens on endothelial cells.
http://www.ncbi.nlm.nih.gov/pubmed/15288766#

Palmitoylation-dependent estrogen receptor alpha membrane localization: regulation by 17beta-estradiol.
http://www.ncbi.nlm.nih.gov/pubmed/15496458

Role of ERbeta palmitoylation in the inhibition of human colon cancer cell proliferation.
http://www.ncbi.nlm.nih.gov/pubmed/17395984

S-palmitoylation modulates estrogen receptor alpha localization and functions.
http://www.ncbi.nlm.nih.gov/pubmed/16274718

Estrogen receptor signalling: bases for drug actions.
http://www.ncbi.nlm.nih.gov/pubmed/16178790

Starting off at page #137 to #147 is some very interesting research (page 142, is IMO one of the best inside the program lotus thread).
http://www.breastnexus.com/showthread.php?tid=17436&page=141

Minireview: The Androgen Receptor in Breast Tissues: Growth Inhibitor, Tumor Suppressor, Oncogene?
http://www.ncbi.nlm.nih.gov/pmc/articles...rt=classic
Credit Clelia for this research article (thanks)

Estrogen receptor signalling: bases for drug actions.

Abstract
Estrogen receptors (ERalpha and ERbeta) mediate the effects of 17beta-estradiol (E2) and account for E2 role on growth, development, and homeostasis maintenance in different tissues and organs. ERalpha and ERbeta function as ligand-dependent transcription factors which directly bind to specific estrogen responsive element (ERE) present into DNA and, in turn, regulate the transcription of E2-sensitive genes. In addition, ERalpha and ERbeta, without direct binding to DNA, regulate transcription indirectly by binding to other transcription factors activating or inactivating the transcription of E2-dependent-ERE-devoid genes. Along with these two E2 mechanisms, it has been recently uncovered that a third signalling pathway, involving cytoplasmic proteins and rapid membrane-initiated responses, serves largely for mitogenic E2-induced effects. The commitment of ERbeta in these rapid E2-induced effects is openly debated. This review will focus and summarize the latest findings regarding the multiple E2 molecular mechanisms and underlines the development of our understanding of anti-cancer drugs acting as ER signalling modulators.

Ok, I'll give it a shot, let's use women's androgens as an example , the major androgen in women is androstenedione, and it takes a pathway to testosterone through the androstenedione pathway to estrogen, with a slight detour (and I mean slight, hard to detect) DHT. The scale tips this pathway towards estrogen, part of what keeps females female. This pathway in males is consider a backdoor pathway, but because DHT is so much stronger it dominates through the standard pathway of testosterone and then enzyme 5 alpha reductase gives it a pass to DHT, unless we intercept it through another enzyme called aromatase, which will then convert to estrogen. But the odds are stacked against us unless preventive actions (anti-androgens) aren't out in place. I like to think of this 3 alpha-hydroxysteroid dehydrogenase" or 3b-Adoil for short, as booby trap (pun) for DHT to find along its pathway (downstream if you will).

In between the androgen pathway sits these booby traps (like light switches), that can block DHT. And so far the only thing I saw to prevent this was cortisteriods, (this action is more complicated I'm afraid too) to prevent this, but I don't think that's the end of the story yet, there's always new research coming out, and by this I mean in the way of cancer treatments, e.g. androgen blockade therapies, new trails etc. just a matter of time before its figured out.......hopefully I'll turn something up soon.

List of Corticosteroid Medications
http://www.livestrong.com/article/27014-...dications/

Here's the techinical version, and I'm sorry if here's where I lose yah.

Four human aldo-keto reductases (AKRs) that belong to the AKR1C subfamily function in vitro as 3-keto-, 17-keto- and 20-ketosteroid reductases or as 3alpha-, 17beta- and 20alpha- hydroxysteroid oxidases to varying degrees. By acting as ketosteroid reductases or hydroxysteroid oxidases these AKRs can either convert potent sex hormones (androgens, estrogens and progestins) into their inactive metabolites or they can form potent hormones by catalyzing the reverse reaction. In this manner they may regulate occupancy and trans-activation of steroid hormone receptors.

From an earlier post,


DHT has an estrogenic action,

The existence of this estrogenic DHT metabolite has raised the possibility that estradiol may not be the major estrogen in males [29]. For instance, in the prostate there is a growing body of evidence that 3β-diol, acting through ERβ, may regulate important physiological events.


Recent data have shown that DHT may be converted into 5α-androstane- 3β-17β-diol (3β-diol) in a virtually irreversible reaction. Once considered inactive, 3β-diol is present in high concentrations in the male and indeed has biological activity. However, 3β-diol does not bind to the androgen receptor (AR), but rather to ERα and ERβ, with higher affinity for ERβ. Based upon these findings, we hypothesized that the modulation of AQP9 by DHT could be indirectly mediated by 3β-diol.

---------------------------

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1615873/


Effects of 3-beta-diol, an androgen metabolite with intrinsic estrogen-like effects,

Abstract

Background: Fluid homeostasis is critical for normal function of the male reproductive tract and aquaporins (AQP) play an important role in maintenance of this water and ion balance. Several AQPs have been identified in the male, but their regulation is not fully comprehended. Hormonal regulation of AQPs appears to be dependent on the steroid in the reproductive tract region. AQP9 displays unique hormonal regulation in the efferent ductules and epididymis, as it is regulated by both estrogen and dihydrotestosterone (DHT) in the efferent ductules, but only by DHT in the initial segment epididymis. Recent data have shown that a metabolite of DHT, 5-alpha- androstane-3-beta-17-beta-diol (3-beta-diol), once considered inactive, is also present in high concentrations in the male and indeed has biological activity. 3-beta-diol does not bind to the androgen receptor, but rather to estrogen receptors ER-alpha and ER-beta, with higher affinity for ER-beta. The existence of this estrogenic DHT metabolite has raised the possibility that estradiol may not be the only estrogen to play a major role in the male reproductive system. Considering that both ER-alpha and ER-beta are highly expressed in efferent ductules, we hypothesized that the DHT regulation of AQP9 could be due to the 3-beta-diol metabolite.

Methods: To test this hypothesis, adult male rats were submitted to surgical castration followed by estradiol, DHT or 3-beta-diol replacement. Changes in AQP9 expression in the efferent ductules were investigated by using immunohistochemistry and Western blotting assay.

Results: Data show that, after castration, AQP9 expression was significantly reduced in the efferent ductules. 3- beta-diol injections restored AQP9 expression, similar to DHT and estradiol. The results were confirmed by Western blotting assay.

Conclusion: This is the first evidence that 3-beta-diol has biological activity in the male reproductive tract and that this androgen metabolite has estrogen-like activity in the efferent ductules, whose major function is the reabsorption of luminal fluids.





a) It has been shown that 3β-diol may have hormonal activity, not acting through the AR, but rather as a ligand for both ERα and ERβ.

b) 3β-diol has higher affinity for ERβ [31], which is abundant in the efferent ductule epithelium [40].

c) In human testis, the 3β-diol concentration is higher than DHT and estradiol [44,45]. It is reasonable to postulate that high concentrations of this metabolite may enter the lumen of efferent ductules.

d) The existence of this estrogenic DHT metabolite has raised the possibility that estradiol may not be the major estrogen in males [29]. For instance, in the prostate there is a growing body of evidence that 3β-diol, acting through ERβ, may regulate important physiological events [26,28,32,46].

Also noteworthy is the fact that 3β-diol stimulates ERβ induced transcriptional activity equal to the cognate ligand estradiol, and the transcriptional selectivity of 3β-diol for ERβ is much greater than its binding selectivity [30,46]

-----------------------------


Concentrations of aromatase and estradiol in the prostate are low, indicating that estradiol may not be the only estrogenic molecule to play a role in the prostate. It is known that DHT can be metabolized to 5alpha-androstane-3beta,17beta-diol (3beta-diol), a hormone that binds to ERbeta but not to AR. The concentration of 3beta-diol in prostate is much higher than that of estradiol. Based on the high concentration of 3beta-diol and since this metabolite is a physiological ERbeta ligand, we hypothesized that 3beta-diol would be involved in the regulation of ERbeta expression.





An endocrine pathway in the prostate, ERbeta, AR, 5alpha-androstane-3beta,17beta-diol, and CYP7B1, regulates prostate growth.
http://www.ncbi.nlm.nih.gov/pubmed/12370428

I've spent more time researching on this backdoor estrogenic action of DHT, aka estrogen receptor beta. From what I see when DHT is metabolized in the liver we can force it to this ER-b back door, thereby lessening (or inactivating) it's potential. And imo cortisteriods inactivates DHT.

Hmmmm so is reishi still good to take? i guess taking everything in moderation is always better but NBE is such a long journey thus everything will be kind of long term type

I forget to include these studies, although somewhat technical it's still some solid info on reishi:


Ganoderma lucidum: A Potent Pharmacological Macrofungus
http://www.researchgate.net/profile/Prakash_Bisen/publication/40032434_Ganoderma_lucidum_a_potent_pharmacological_macrofungus/links/0fcfd505b4749c887f000000.pdf?ev=pub_ext_doc_dl&origin=publication_detail&inViewer=true


Ganoderma – A therapeutic fungal biofactory
http://www.researchgate.net/profile/Russell_Paterson/publication/6882609_Ganoderma_-_a_therapeutic_fungal_biofactory/links/00b7d5225ef366b7c6000000.pdf?ev=pub_ext_doc_dl&origin=publication_detail&inViewer=true


Target proteins of ganoderic acid DM provides clues to various pharmacological mechanisms:
http://www.nature.com/srep/2012/121130/s...p00905.pdf

______________________________

Other info:

Effect of epidermal growth factor and prostaglandin on the expression of aromatase (CYP19) in human adrenocortical carcinoma cell line NCI-H295R cells
http://joe.endocrinology-journals.org/co...9.full.pdf

Comparative effects of DHEA vs. testosterone, dihydrotestosterone, and estradiol on proliferation and gene expression in human LNCaP prostate cancer cells
http://ajpendo.physiology.org/content/aj...3.full.pdf

Nutritional Influences on Estrogen Metabolism
http://www.afmcp-sa.com/ansr/MET451%20En...20ANSR.pdf

yep, maybe in men the estrogenic activity of soy is more effective than in women, but also it depends on individual genetics. You'll see in the link below, a very good article that summarize a lot of papers about phytoestrogens. After reading that, you can just say: yes, it could wbe helpful as it could be harmful... and maybe it's wise stay in the middle, not exceed:
http://foodforbreastcancer.com/foods/gen...d-daidzein

an extract of the article: (here it is something in english about equol and its conversion

Equol has been shown to have the strongest binding affinities and estrogenic activities (especially for ERβ) among the daidzin metabolites and has been hypothesized to be largely responsible for the estrogen-like activities of soy and its isoflavones. However, there is a great deal of variation among individuals in the metabolism of genistin and daidzin, which appears to be dependent partly on environmental factors, including other components of the diet, and partly on genetic factors.

Only 25% to 35% of the U.S. Caucasian population is capable of converting daidzein to equol, whereas people in high soy consumption areas of Asia have rates closer to 40% to 60%. There is some evidence that Hispanic or Latino women are also more likely to be equol producers. Approximately 80% to 90% of people harbor the bacteria required to produce ODMA. The frequency of equol producers in one study of vegetarians was found to be 59%, similar to the reported frequency in Japanese adults consuming soy, and much higher than for nonvegetarian adults (25%). One Japanese study found that consumption of dairy products was significantly higher in those who did not excrete equol than in those who did.



other papers that i looked at today:

http://www.ncbi.nlm.nih.gov/pubmed/25789108

http://www.ncbi.nlm.nih.gov/pubmed/25673549

http://www.ncbi.nlm.nih.gov/pubmed/25338271

http://www.ncbi.nlm.nih.gov/pubmed/25302172

http://www.ncbi.nlm.nih.gov/pubmed/25263312

http://www.ncbi.nlm.nih.gov/pubmed/25236805

isoflavones in the brain: http://www.ncbi.nlm.nih.gov/pubmed/25232349

http://www.ncbi.nlm.nih.gov/pubmed/22510793

http://www.ncbi.nlm.nih.gov/pubmed/25592466

http://www.ncbi.nlm.nih.gov/pubmed/24504368

http://www.ncbi.nlm.nih.gov/pubmed/24531783

http://www.ncbi.nlm.nih.gov/pubmed/24053483

Oh yeah ......you know I'll want to talk about this research studies , their just screaming "hey I'm here, read me" ......solve me......

Structure, function and tissue-specific gene expression of 3β-hydroxysteroid dehydrogenase/5-ene-4-ene isomerase enzymes in classical and peripheral intracrine steroidogenic tissues.
________________________________________
data indicate that the presence of multiple 3β-HSD isoenzymes offers the possibility of tissue-specific expression and regulation of this enzymatic activity that plays an essential role in the biosynthesis of all hormonal steroids in classical as well as peripheral intracrine steroidogenic tissues.

http://www.ncbi.nlm.nih.gov/pubmed/22217825

Bovine adrenal 3beta-hydroxysteroid dehydrogenase (E.C. 1.1.1. 145)/5-ene-4-ene isomerase (E.C. 5.3.3.1): characterization and its inhibition by isoflavones.
____________________________________________
The isoflavones daidzein, genistein, biochanin A and formononetin inhibit potently and preferentially the gamma-isozymes of mammalian alcohol dehydrogenase (gammagamma-ADH), the only ADH isozyme that catalyzes the oxidation of 3beta-hydroxysteroids. Based on these results, we proposed that these isoflavones might also act on other enzymes involved in 3beta-hydroxysteroid metabolism. Recently, we showed that they indeed are potent inhibitors of a bacterial beta-hydroxysteroid dehydrogenase (beta-HSD). To extend this finding to the mammalian systems, we hereby purified, characterized and studied the effects of isoflavones and structurally related compounds on, a bovine adrenal 3beta-hydroxysteroid dehydrogenase (3beta-HSD). This enzyme catalyzes the oxidation of 3beta-hydroxysteroids but not 3alpha-, 11beta- or 17beta-hydroxysteroids. The same enzyme also catalyzes 5-ene-4-ene isomerization, converting 5-pregnen 3, 20-dione to progesterone. The K(m) values of its dehydrogenase activity determined for a list of 3beta-hydroxysteroid substrates are similar (1 to 2 microM) and that of its isomerase activity, determined with 5-pregnen 3, 20-dione as a substrate, is 10 microM. The k(cat) value determined for its isomerase activity (18.2 min(-1)) is also higher than that for its dehydrogenase activity (1.4-2.4 min(-1)). A survey of more than 30 isoflavones and structurally related compounds revealed that daidzein, genistein, biochanin A and formononetin inhibit both the dehydrogenase and isomerase activity of this enzyme. Inhibition is potent and concentration dependent. IC(50) values determined for these compounds range from 0.4 to 11 microM, within the plasma and urine concentration ranges of daidzein and genistein of individuals on vegetarian diet or semi-vegetarian diet. These results suggest that dietary isoflavones may exert their biological effects by inhibiting the action of 3beta-HSD, a key enzyme of neurosteroid and/or steroid hormone biosynthesis.
http://www.ncbi.nlm.nih.gov/pubmed/10704908

estrogenic isoflavones are potent inhibitors of beta-hydroxysteroid dehydrogenase of P. testosteronii.
___________________________________________
The isoflavones daidzein, genistein, biochanin A and formononetin selectively inhibit the gamma-isozymes of mammalian alcohol dehydrogenase (ADH). Since gamma-ADH is the only ADH isoform that catalyzes 3 beta-hydroxysteroid oxidation, it was conjectured that these isoflavones might also inhibit other enzymes involved in 3 beta-hydroxysteroid metabolism. P. testosteronii beta-hydroxysteroid dehydrogenase (beta-HSD) was used to evaluate this hypothesis. Indeed, all isoflavones that inhibit gamma-ADH were found to be potent inhibitors of beta-HSD. Both the 3 beta- and 17 beta-HSD activities of the enzyme are inhibited. Kinetic analyses with pregnenolone (3-beta-OH) and testosterone (17-beta-OH) as substrates reveal that daidzein and genistein inhibit beta-HSD competitively with respect to the sterol substrates. Their Ki values are very similar and range from 0.013 to 0.02 microM. These results suggest that isoflavones may exert some of their biological effects by modulating activities of enzymes that metabolize steroids critical to hormonal and/or neuronal functions.
http://www.ncbi.nlm.nih.gov/pubmed/7488041#

What i do not understand up there underlined is:
why addiction of DHT didn't decrease gland morphology in adult mammary gland?
why affected just the midpuberty, retarding development?
maybe in the adult mammary gland, DHT in extra amount, is it converted in 3-diol? so it can neutralize is own androgenic effect? I don't know...maybe it's that back-door effect, but result is not estrogenic, otherwise mammary gland should have developed..

I could understand just flutamide action... in midpuberty should work less because of less presence of AR receptor. When AR receptors increase in post-puberty, the antagonism of them promote growing.

If we low DHT, we should mimic a bit flutamide action. And also, more testosterone will be converted in estradiol, as mentioned in your sign

Hi Clelia,

Hope you had a good weekend,

Sorry I jumped ahead a few spots, getting back to your question. 3b-diol does explain the back door response. I'm just wondering if there's a re-absorption response before being excreted?, (e.g. re-activate DHT, one more time) as seen with estrogen metabolites. I dunno?,

But in males it does seem that 3-diol has estrogen action (ER-b) in epithelia of efferent ductules and the epididymis. I'm going to post about 4-5 posts regarding this process (male ER-b) that I posted a few months ago if that's ok. If rather focus on mammary DHT's fine too, either way, there's much to solve with your help.

So what if there was way to influence an estrogen action in the Leydig cells since they already include estrogen receptors. Well, a pathway needs to be established. Here is one possible source, or could be a possible action.

Sperm, a source of estrogen
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1518866/
Environ Health Perspect. Oct 1995; 103(Suppl 7): 59–62.
PMCID: PMC1518866
Research Article
Sperm, a source of estrogen.

Other info: it's being researched already.

Estrogen signaling in testicular cells.

Aromatase transforms irreversibly androgens into estrogens and is present in the endoplasmic reticulum of various tissues including the mammalian testis. In rat all testicular cells except peritubular cells express aromatase. Indeed in adult rat germ cells (pachytene spermatocytes and round spermatids) we have demonstrated the presence of a functional aromatase (transcript, protein and biological activity) and the estrogen output is equivalent to that of Leydig cells. In addition in the adult rat, transcripts of aromatase vary according to the germ cell type and to the stages of seminiferous epithelium. By contrast with the androgen receptors mainly localized in somatic cells, estrogen receptors (ERs) are described in most of the testicular cells including germ cells. Moreover, besides the presence of high affinity ERα and/or ERβ, a rapid membrane effect has been recently reported and we demonstrated that GPR30 (a transmembrane intracellular estrogen receptor) is expressed in adult rat pachytene spermatocytes. Therefore estrogens through both GPR30 and ERα are able to activate the rapid EGFR/ERK/c-jun signaling cascade, which in turn triggers an apoptotic mitochondrial pathway involving an increase in Bax expression and a concomitant reduction of cyclin A1 and B1 gene levels. In another study in round spermatids of adult rat we have shown that the rapid membrane effect of estradiol is also efficient in controlling apoptosis and maturation / differentiation of these haploid germ cells. In man the presence of a biologically active aromatase and of estrogen receptors has been reported in Leydig cells, but also in immature germ cells and ejaculated spermatozoa. Thus the role of estrogen (intracrine, autocrine and / or paracrine) in spermatogenesis (proliferation, apoptosis, survival and maturation) and more generally, in male reproduction is now evidenced taking into account the simultaneous presence of a biologically active aromatase and the widespread distribution of estrogen receptors especially in haploid germ cells.

oK then I just have to ask...
Would men's sperm be a significant source of aromatase?

I think so, the study concluded that Leydig cells, germ cells, and seminiferous tubules all showed positive stains for aromatase. But it has to do more with the head (tip) of sperm.

I take that back, it's the tail that has the most aromatase and the head of the epididymis displays estrogen receptors where estrogen synthesis occurs.

Summary diagram of potential estrogen action in epithelia of efferent ductules and the epididymis. At least 4 potential pathways are considered. 1) testosterone (T) can enter the cell or be converted to E2 by aromatase (Arom) found in luminal sperm [54]. Testosterone binds AR and translocates into the nucleus, where it binds to AREs, on the promoter regions of genes with or without EREs. 2) E2 will either enter the cell, as did testosterone or bind the membrane ESR (mESR1). It remains controversial whether E2 binds GPR30 in the membrane [144] or collaborates with mESR1 to mediate epidermal growth factor receptor (EGFR) activation (nonclassical) of kinases and phosphorylation [180]. It is well known that E2 binds ESR1 and translocates into the nucleus for classical mediation of transcription through EREs and recruitment of numerous cofactor proteins (C1–3). It is unknown how AR and ESR1 compete for these cofactors, or what happens when the steroid balance is altered in a cell expressing both receptors. 3) The ESR1 can also be activated through phosphorylation and mediate transcription through the ERE. 4) It is well documented in other tissues that mESR1 binds E2, resulting in very rapid cell signaling [84, 175, 178]. This rapid steroid activity through the membrane receptor involves caveolin-1, G proteins, and the phosphorylation/dephosphorylation cascades, which mediate transcription either through the ESR1/ERE or other transcription factors (TF).
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3071263/


I think we made an important step in solving the Estrogen action in Genetic Males and NBE.

Or a 67 yard field goal.

Clelia,
The part of the re-absorption might come from Aldo-keto reductases (AKRs), what do you think?.
Example:

Type 3 3alpha-hydroxysteroid dehydrogenase (aldo-keto reductase 1C2, aka-AKR acts solely as a reductase to convert 5alpha-dihydrotestosterone (DHT), a potent ligand for the AR

_____________________________________________

It's like deconstructing a model (call it a airplane model) that someone else built, only you're working in reverse to deconstruct right. Same applies here, you see a study that states 5 alpha reductase is reduced in the liver, now maybe this study was for cancer research or something similar. Let's take one of these studies,

Role of human type 3 3alpha-hydroxysteroid dehydrogenase (AKR1C2) in androgen metabolism of prostate cancer cells.

Aldo-keto reductases (AKRs) is another superfamily class of enzymes like the Cytochrome P450 enzyme super family, which are present in most tissues of the body, and play important roles in hormone synthesis and breakdown (including estrogen and testosterone synthesis and metabolism), cholesterol synthesis, and vitamin D metabolism. Cytochrome P450 enzymes also function to metabolize potentially toxic compounds, including drugs and products of endogenous metabolism such as bilirubin, principally in the liver.

AKRs are involved in the development and progression of many cancers, as well as chemotherapeutic drug resistance. AKR1B1 and AKR1B10 are overexpressed in tumors, such as liver, breast, and lung cancer. Several AKRs (AKR1A1, AKR1B10, and AKR1C1-3) are involved in tobacco-carcinogenesis, but they also catalyze the detoxication of nicotine derived nitrosamino ketones. In addition, AKR1C1-3 enzymes play a key role in the regulation of proliferative signaling in hormone dependent cancers.

So what they did in this study was to cut off the androgen synthesis to the receptors using another steroid , Four human aldo-keto reductases (AKRs) that belong to the AKR1C subfamily function in vitro as 3-keto-, 17-keto- and 20-ketosteroid reductases or as 3alpha-, 17beta- and 20alpha- hydroxysteroid oxidases to varying degrees. By acting as ketosteroid reductases or hydroxysteroid oxidases these AKRs can either convert potent sex hormones (androgens, estrogens and progestins) into their inactive metabolites or they can form potent hormones by catalyzing the reverse reaction. In this manner they may regulate occupancy and trans-activation of steroid hormone receptors.

In English, I want to find the link to activate AKR1c in the liver to shut off the androgen receptors therefore DHT never gets activated, simple right?.

Regulates access of 5alpha-DHT to the androgen receptor.

Abstract
Pairs of hydroxysteroid dehydrogenases (HSDs) govern ligand access to steroid receptors in target tissues and act as molecular switches. By acting as reductases or oxidases, HSDs convert potent ligands into their cognate inactive metabolites or vice versa. This pre-receptor regulation of steroid hormone action may have profound effects on hormonal response. We have identified the HSDs responsible for regulating ligand access to the androgen receptor (AR) in human prostate. Type 3 3alpha-hydroxysteroid dehydrogenase (aldo-keto reductase 1C2, aka-AKR acts solely as a reductase to convert 5alpha-dihydrotestosterone (DHT), a potent ligand for the AR (K(d)=10(-11)M for the AR), to the inactive androgen 3alpha-androstanediol (K(d)=10(-6)M for the AR); while RoDH like 3alpha-HSD (a short-chain dehydrogenase/reductase (SDR)) acts solely as an oxidase to convert 3alpha-androstanediol back to 5alpha-DHT. Our studies suggest that aldo-keto reductase (AKRs) and SDRs function as reductases and oxidases, respectively, to control ligand access to nuclear receptors.
http://www.ncbi.nlm.nih.gov/pubmed/17223255

Notice how Aldo-keto reductases (AKRs) position themselves between DHT and 3-diols, this is where the estrogenic action takes place. These actions of AKR1C's takes place in androgen metabolism of the prostate.

Aldo-keto reductases (AKRs) is another superfamily class of enzymes like the Cytochrome P450 enzyme super family.






Estrogen receptor β and 17β-hydroxysteroid dehydrogenase type 6, a growth regulatory pathway that is lost in prostate cancer

Estrogen receptor β (ERβ) is activated in the prostate by 5α-andros- tane-3β,17β-diol (3β-Adiol) where it exerts antiproliferative activity. The proliferative action of the androgen receptor is activated by 5α- dihydrotestosterone (DHT). Thus, prostate growth is governed by the balance between androgen receptor and ERβ activation. 3β- Adiol is a high-affinity ligand and agonist of ERβ and is derived from DHT by 3-keto reductase/3β-hydroxysteroid dehydrogenase en- zymes. Here, we demonstrate that, when it is expressed in living cells containing an estrogen response element-luciferase reporter, 17β-hydroxysteroid dehydrogenase type 6 (17βHSD6) converts the androgen DHT to the estrogen 3β-Adiol, and this leads to activation of the ERβ reporter. This conversion of DHT occurs at concentrations that are in the physiological range of this hormone in the prostate. Immunohistochemical analysis revealed that 17βHSD6 is expressed in ERβ-positive epithelial cells of the human prostate and that, in prostate cancers of Gleason grade higher than 3, both ERβ and 17βHSD6 are undetectable. Both proteins were present in benign prostatic hyperplasia samples. These observations reveal that for- mation of 3β-Adiol via 17βHSD6 from DHT is an important growth regulatory pathway that is lost in prostate cancer.

http://www.ncbi.nlm.nih.gov/pmc/articles...117772.pdf

_________________________________________________

As you can see the pathway for Testosterone, Approximately 7% of testosterone is reduced to 5α-dihydrotestosterone (DHT) by the cytochrome P450 enzyme 5α-reductase, an enzyme highly expressed in male sex organs and hair follicles. Approximately 0.3% of testosterone is converted into estradiol by aromatase (CYP19A1) an enzyme expressed in the brain, liver, and adipose tissues. Note-the percentages are slightly off, (multiple sources).

By inhibiting the enzyme 5-alpha reductase and promoting the enzyme aromatase along with your choice phytoestrogens or pharma E is key for breast growth in bio-males.

Herbs that convert aromatase-White Peony, Liorice root, Genistein (PM), BO.

Herbs that help block 5 ar, Licorice root, WP, Reishi, SP, pygeum, nettle root (NR is tricky though), BO (not an herb), chinese skullcap, linolenic acid, green tea, progesterone cream is a strong 5 ar, pumpkin seed oil, linolenic acid.

(Pharma-Dutasteride and Finasteride). Both finasteride and dutasteride undergo extensive hepatic metabolism primarily via the cytochrome P450 3A4 (CYP 3A4) isoenzyme system.

Bruno deLignieres, an impeccable French researcher and Thiery Hertoghe, MD, fourth generation in the most distinguished family of endocrinologists in Belgium, have put forth the notion that rising estrogen levels are more likely to be the initiator of the process and that testosterone and DHT may then be a secondary player (promoter). In fact, phytotherapy (large doses of phytoestrogens - soy) is commonly used in European medical practices to treat BPH.

(Jonathan Wright and Eugene Shippen have written excellent, and popular books, discussing these more far-sighted notions all too commonly overlooked and even rejected in current conventional American Medical thinking.)

Testosterone is reduced by the enzyme 5-a-reductase to DHT which is then thought to be the real culprit. The argument between the use of Saw Palmetto, Pygeum and Pumpkin seeds vs Proscar are both directed at blocking this enzyme. Strangely, DHT is most important for sexual vigor, so blocking this step may have some unintended consequences!

On the other hand, Testosterone is also converted into estradiol by aromatase (producing the aromatic ring). This occurs increasingly with age in the liver but most importantly ... in the fat stores.

http://www.antiaging.com/andropause/andropause2.html

Its been stated here before that the Androgen to Estrogen pathway is easier than the Testosterone to Estrogen pathway, and once again aromatase continues to demonstrate the factual evidence.

A couple of French researchers recently reported this:

Testosterone is reduced by the enzyme 5-a-reductase to DHT which is then thought to be the real culprit. The argument between the use of Saw Palmetto, Pygeum and Pumpkin seeds vs Proscar are both directed at blocking this enzyme. Strangely, DHT is most important for sexual vigor, so blocking this step may have some unintended consequences!

On the other hand, Testosterone is also converted into estradiol by aromatase (producing the aromatic ring). This occurs increasingly with age in the liver but most importantly ... in the fat stores.
Now you see the connection. As we age, and frequently gain increasing fat stores, we are feeding the aromatase connection, increasing our estradiol levels and if this theory holds, increasing the promotion of prostate disease.

Also that rising estrogen levels are more likely to be the initiator of the process and that testosterone and DHT may then be a secondary player (promoter). In fact, phytotherapy (large doses of phytoestrogens - soy) is commonly used in European medical practices to treat BPH.

Another example of the androgen/estrogen pathway:



http://www.antiaging.com/andropause/andropause2.html

[/quote]

That's a good find, Clelia. Thanks!

happy you appreciate, you're welcome

what's your opinion?, sorry.... I've listed like 10 issues lol.

yep, lot of stuff to read here ... i'm reading everything you reported.
I will answer later on.

The first thing that I want to say is...
I spent an afternoon trying to understand this:

In this study, we investigated whether development of the murine mammary gland could be altered by stimulating or suppressing androgen receptor (AR) signaling in vivo. Intact virgin female mice aged 5 wk (midpuberty) or 12 wk (postpuberty) were implanted with slow-release pellets containing either placebo, 5α-dihydrotestosterone (1.5 mg) or the AR antagonist flutamide (60 mg). Treatment with 5α-dihydrotestosterone from midpuberty to 12 wk of age-retarded ductal extension by 40% (P = 0.007), but treatment from 12-21 wk had no significant effect on gland morphology. In contrast, inhibition of AR signaling with flutamide from midpuberty had no effect on the mammary gland, but flutamide treatment from 12-21 wk increased ductal branching (P = 0.004) and proliferation (P = 0.03) of breast epithelial cells. The increased proliferation in flutamide-treated mice was not correlated with serum estradiol levels or estrogen receptor-α (ERα) expression.

http://www.ncbi.nlm.nih.gov/pubmed/21846805

moreover: In control mice, the frequency and intensity of AR immunostaining in mammary epithelial cells was significantly increased in the 12- to 21-wk treatment group compared with the 5- to 12-wk group (P < 0.001). In contrast, no change in ERα occurred, resulting in a marked increase in the AR to ERα ratio from 0.56 (±0.12) to 1.47 (±0.10).
--> this means that receptor ERalfa is in the same quantity, in midpuberty and postpuberty. In contrast, AR receptor triple from middlepuberty to post-puberty, and that's why breast stop to grow in female (because AR receptors increase a lot).

Also we see from your favourite article that male rats depleted of AR receptors, develop full mammary gland.

So we see how important is AR signals in breast size (despite everything else).

What i do not understand up there underlined is:
why addiction of DHT didn't decrease gland morphology in adult mammary gland?
why affected just the midpuberty, retarding development?
maybe in the adult mammary gland, DHT in extra amount, is it converted in 3-diol? so it can neutralize is own androgenic effect? I don't know...maybe it's that back-door effect, but result is not estrogenic, otherwise mammary gland should have developed..

I could understand just flutamide action... in midpuberty should work less because of less presence of AR receptor. When AR receptors increase in post-puberty, the antagonism of them promote growing.

If we low DHT, we should mimic a bit flutamide action. And also, more testosterone will be converted in estradiol, as mentioned in your sign

Circulating 2-hydroxy and 16-α hydroxy estrone levels and risk of breast cancer among postmenopausal women

Thank you about this information, i read the abstract but i didn't get it... it talks about a ratio between two components, but i don't see what ratio. I will open the pdf... but not now... (no time left), btw, do you know if there is something that low this risk?

On another note....I've seen that EPA and DHA reduces the risk of breast cancer by as much as a 32% reduction, I don't know the dosage.

the article you posted says:
"The purpose of the WHEL Study was to assess whether a major increase in vegetable, fruit, and fiber intake and a decrease in dietary fat intake reduces the risk of recurrent and new primary breast cancer and all-cause mortality among women with previously treated early-stage breast cancer.
Women with higher intakes of EPA and DHA from food had an approximate 25% reduced risk of additional breast cancer events, compared with the lowest tertile of intake. Women with higher intakes of EPA and DHA from food had a dose-dependent reduced risk of all-cause mortality. EPA and DHA intake from fish oil supplements was not associated with breast cancer outcomes. The investigation indicates that marine fatty acids from food are associated with reduced risk of additional breast cancer events and all-cause mortality. J. Nutr. 141: 201–206, 2011."
maybe you can find the answer at your question in this table:

" Anti-androgenic activity of fatty acids." http://www.ncbi.nlm.nih.gov/pubmed/19353546 (2009)

Great link, thank you so much, I can only think of two supplements that cam meet that demand........coconut oil and EPO-evening primrose oil.

and hemp seed oil

I've got to go now. I know that i still miss something, i'll come back next week, i'm off for the weekend. see you!

Hi Lotus, i like reading your posts, now I have no much time to answer, but I can tell you something

Thanks Clelia, , I appreciate your time.

Research is often controversial, because maybe in different studies there are differences that could affect results (for example, in vivo and in vitro can change final results).

Great point, I noticed limitations in some studies (e.g. available test samples w/regards to country's ban or limitations) could affect results, but I understand what you mean.

Also, we should take account of the target of the subject: different tissues can respond in different ways, with same inizial conditions. This is due to the variability of the receptor expressed in every tissue, which often are not the same and in same amount (understandably).

Ok, Like multiple response, or unintended consequence.

So, your research about the "estrogen DHT metabolite", is based on prostate, not breast tissue or skin. That's why men become bald: there is androgen dominance in their skin, and fighting DHT is proved good to grow hair.
Also, the DHT metabolite, interacts with ERb, and we know that alfa is better for breast growth, isnt it?

BPH/prostate research does seemed skewed towards 5-ar inhibitors/ anti DHT. Since the prostate is pro ER-a it seems likely estrogen could be a mediator of cancers too.

Its good to try to convert DHT in estrogen metabolite, but i think its better to shut it down, at least for breast growth.

I've seen some promising research that includes androgen blockade therapy, 17beta -HSD, even using prolactin molecules to box out DHT because of their larger size, suggesting to me PRL is DHT inhibitor. But I think COX is also an aromatase at PGE.

And if you do this, what about your prostate risk? Since the metabolite help prevent prostate cancer, what if you low it? I think you should read this also, maybe there are other mechanisms involved, in prostate cancer:

Yes, elimaniting androgen/DHT ip even in Mtf has long term consequence. The biological affects of androgens are are still needed. The assumptation of testosterone being poison is often misinterpreted. Testosterone is the sex hormone that converts to all estrogens, without T Mtf wouldn't make the necessary conversion to transition. I think it's a mistake to reduce testosterone, the reduction is needed at DHT...... and the reason is quite obvious.

" Anti-androgenic activity of fatty acids." www.ncbi.nlm.nih.gov/pubmed/19353546 (2009)

Great link, thank you so much, I can only think of two supplements that cam meet that demand........coconut oil and EPO-evening primrose oil.

The question we should be asking is how much......

As in how much Testosterone (DHT) do I need to overcome daily, or how much estradiol besides my .3 mg I produce daily is needed.

Here's what I mean--

According to the National Institutes of Health, the normal range of testosterone is 30 to 95 nanograms per deciliter (ng/dL) for women and 300 to 1,200 ng/dL for men, but individual laboratories might have a slightly different range that they consider normal. Also keep in mind that the levels vary with age. In women, the level of testosterone in the blood is lowest during puberty and adolescence, and is highest in pre- and post-menopausal women. For men, the levels increase during puberty and stay steady for much of their young adult life. They then slowly begin to decline during middle and older age.
http://www.livestrong.com/article/239396...r-a-woman/


Men and women produce exactly the same hormones, but in different amounts: as a rule, men produce 20 times more testosterone than women, while women produce more estrogen and progesterone. As with most things in nature, this "norm" can become imbalanced, and some women may have higher levels of testosterone, causing a unique set of symptoms.

Daily averages-

Endogenous avg. produced daily (males)

MEN
-Hormone ( FSH): 2 - 18 mIU/ml
-Testosterone 3mg to 10mg (daily)
-Prolactin 7 - 18 ng/ml
-FT-Free T is about 2% (this is the functional T)
-BT-Bound T or 98%
-Albumin 38% (bloodstream)
-SHBG is 60% (sex-hormone-binding-globulin)
-DHT approximately 7% of T is reduced by 5 ar
-Estradiol approximately 0.3% of testosterone is converted into E2 by aromatase (CYP19A1) of that 0.3%, 20% is directly produced by the testes. Roughly 60% of circulating estradiol is derived from direct testicular secretion or from conversion of testicular androgens. The remaining fraction is derived from peripheral conversion of adrenal androgens. The serum levels of estradiol in males (14 - 55 pg/mL) are roughly comparable to those of postmenopausal women (< 35 pg/mL).

Endogenous avg. produced daily (females)

WOMEN
-Testosterone 0.05 mg (produced daily)
-FT-Free T normal calculated free testosterone is 0.4 – 0.8 ng/dl (or 40 – 80 pg/dl).
-Albumin 34% bloodstream)
-SHBG is 66% (sex-hormone-binding-globulin)
-Estradiol 70 to 500 mg of estradiol daily, (depending on the phase of the menstrual cycle. This is converted primarily to estrone, which circulates in roughly equal proportion to estradiol, and to small amounts of estriol.)
-Estradiol in postmenopausal women (< 35 pg/mL).
-Progesterone levels tend to be < 2 ng/ml prior to ovulation, and > 5 ng/ml after ovulation. If pregnancy occurs, human chorionic gonadotropin is released maintaining the corpus leuteum allowing it to maintain levels of progesterone.

Avg tests

Hormone Follicular Day of LH Surge Mid-luteal
-Follicle Stimulating (FSH) < 10 mIU/ml > 15 mIU/ml -
-Luteinizing Hormone-(LH) < 7 mIU/ml > 15 mIU/ml -
-Prolactin < 25 ng/ml
-Thyroid Stimulating Hormone 0.4 - 3.8 uIU/ml (TSH)
-Estradiol ( E2) < 50 pg/ml ( Day 3) > 100 pg/ml
-Progesterone < 1.5 ng/ml > 15 ng/ml




Reference Values
Free Estradiol, Percent
Reference Ranges (%)

Adult Males 1.7 - 5.4
Adult Females 1.6 - 3.6

Free Estradiol, Serum
Reference Ranges (pg/mL)

Adult Males 0.2 - 1.5
Adult Females 0.6 - 7.1

Sex Hormone Binding Globulin (SHBG), Serum
Reference Ranges
Adult Males 20 - 60
Adult Female
Premenopausal 40 - 120
Postmenopausal 28 - 112

the most complete list here:
http://wikipedia.org/wiki/Reference_rang...lood_tests

This is very interesting:

Normal Hormone Proportions
http://georgiahormones.com/pdf/Brochure_...rtions.pdf

[Lotus]

Last post, sorry if didn't get to answer the last couple of questions posed. Good luck to all, fair winds and seas. Beam me up Scotty.

Btw, No. 1 favorite research post is when a scientist calls you a scientist.

Hi Lotus, here I am
This is another paper about palmitoylation:

Palmitoylation regulates 17β-estradiol-induced estrogen receptor-α degradation and transcriptional activity.
http://www.ncbi.nlm.nih.gov/pubmed/22446104

[...]
The lack of palmitoylation renders ERα more susceptible to E2-dependent degradation, blocks ERα S118 phosphorylation and prevents E2-induced ERα estrogen-responsive element-containing promoter occupancy. Consequently, ERα transcriptional activity is prevented and the receptor addressed to the nuclear matrix subnuclear compartment. These data uncover a circuitry in which receptor palmitoylation links E2-dependent ERα degradation, S118 phosphorylation, and transcriptional activity in a unique molecular mechanism. We propose that rapid E2-dependent signaling could be considered as a prerequisite for ERα transcriptional activity and suggest an integrated model of ERα intracellular signaling where E2-dependent early extranuclear effects control late receptor-dependent nuclear actions.

ok palmitoylation is good for a good estrogen activity, you ask: "the palmitoylation of estrogen receptor alpha (ER-a) is (or can be) mediated by oxidative phosphorylation?"
my answer is: I don't know...what do you mean?

Oxidative phosphorylation, wiki (not my favourite source, but this time i can use it):
Oxidative phosphorylation (or OXPHOS in short) is the metabolic pathway in which the mitochondria in cells use their structure, enzymes, and energy released by the oxidation of nutrients to reform ATP. Although the many forms of life on earth use a range of different nutrients, ATP is the molecule that supplies energy to metabolism. Almost all aerobic organisms carry out oxidative phosphorylation.[...]. Although oxidative phosphorylation is a vital part of metabolism, it produces reactive oxygen species such as superoxide and hydrogen peroxide, which lead to propagation of free radicals, damaging cells and contributing to disease and, possibly, aging (senescence). The enzymes carrying out this metabolic pathway are also the target of many drugs and poisons that inhibit their activities.


in the paper above, it says: These E2 rapid effects require a population of the ERα located at the cell plasma membrane through palmitoylation, a dynamic enzymatic modification mediated by palmitoyl-acyl-transferases.

We should find how this enzyme palmitoyl-acyl-transferases works, if you want to gain estrogen activity (and maybe is not enough, as you see our bodies are quite complicated... )
indeed from your link: "E2 reduces both ERalpha palmitoylation and its interaction with caveolin-1, in a time- and dose-dependent manner"
So, if you want you can increase estrogen receptor expression, but there is a negative feedback as well from estradiol. This is good for the body, to regulate his pathways....and try to keep some equilibrium. We just want to move some of it to favor breast growth, and if estrogen receptor is stronger than negative feedback of estradiol, than it should be worthy the way of palmitoylation.

I think the best way to try to gain some breast is in my previous link, and you noticed that: we should just low the androgen activity in breast, to have breast growth. This is quite simpler than taking account of all the other biological pathways, that's why i started from that (anyway, everything is important, also estrogen, and food, and enzymes.... but i think that the king to fight here is DHT)
I didn't know about DHT metabolites, my thoughs are: if DHT (and metabolite) is more androgenic, then estrogenic in breast tissue, than it could be helpful low it.

I'm sure you're aware that fatty acids synthesize aromatase, (what are your thoughts?)."

ehm... nope. I'm just a scientist, not omniscient :-P
i didn't find this before. I read something on your A.A. thread, but now i missed it. Could you link some source? I tried to have a look but i couldn't find much.
Then i will tell you what I think, but for sure, if fatty acids can promote aromatase expression, that would be great!

"On another note....I've seen that EPA and DHA reduces the risk of breast cancer by as much as a 32% reduction, I don't know the dosage."

Where did you see that? which paper? i quickly had a look on the one you linked before, but i didn't find that information

thank you Lotus, I'm ready to go. Happy me!
yep you gave to a scientist a good homework

Did i?..... cool, I thought I might have insulted you lol.

no worries, of course not

How come, am I the only one? Where are all the others? There is a lot of people here.

Don't know....but I'm glad you're here. I have all kinds of crazy ideas and only myself to entertain them, lmao."

eheh, i'm glad as well, but there is other people that contributed sometimes. Anyway I understand the way you feel. I'm crazy almost like you, and i like scientific research, so I can make good company (Imao)

Anyway, you could be a scientist.

You think so?, nah....... I'm not worthy although I'd love to be one. and thank you so much for saying so.

Your knowledge is becoming huge, also you research a lot, so there is no big difference between you and a scientist. You could apply to a University if you wanted.

Finally, could you help me? I'm looking information for "bad estrogen" that make growth faster,
what is its name? I saw it somewhere but I don't remember.
Thank you very much
See you,
bye!

thank you Lotus, I'm ready to go. Happy me!
yep you gave to a scientist a good homework. How come, am I the only one? Where are all the others? There is a lot of people here. Anyway, you could be a scientist. Meanwhile I leave to you something as well, that I think you will appreciate (if you havent already read them).

" The Androgen Receptor in Breast Tissues " www.ncbi.nlm.nih.gov/pmc/articles/PMC3404296/ (2012) " Differential effects of exogenous androgen and an androgen receptor antagonist in the peri- and postpubertal murine mammary gland." www.ncbi.nlm.nih.gov/pubmed/21846805 (2011)

bye, see you soon

Wow thanks Clelia,

You've got me motivated now... from those research papers it led me to research posted below, and from that I see DHT is non-aromatizable as we know.....but!!!!......it also create what's known as a second estrogen effect, ER-b mostly though...(pretty cool huh?). I knew it has this back-door effect, and mostly from 3b-doil. and then it would by mostly brain, bone etc end result, but none the less it does have an ER result. Now Sertoli cells on the other hand has a huge aromatase link, by way of spermatozoa.


Estrogen and androgen receptors: Regulators of fuel homeostasis and emerging targets for diabetes and obesity
http://www.ncbi.nlm.nih.gov/pmc/articles...247852.pdf




Metabolic effects of ERα and ERβ activation in females
Activation of ERα in the central nervous system (CNS) suppresses food intake, increases energy expenditure and decreases body weight. In addition, activation of ERα improves peripheral energy and glucose homeostasis in multiple ways by 1) preventing liver steatosis, suppressing hepatic glucose production and improving insulin sensitivity, 2) enhancing skeletal muscle lipid oxidation, GLUT4 expression and insulin sensitivity, 3) enhancing subcutaneous white adipose tissue (WAT) distribution while decreasing overall WAT mass by decreasing WAT free fatty acid (FFA) uptake, lipid synthesis and increasing lipolysis, 4) favoring pancreatic β-cell survival and function by preventing pro-apoptotic injuries and lipotoxicity, and increasing insulin biosynthesis and glucose-stimulated insulin release (GSIS). Activation of ERβ in the central nervous system (CNS) also suppresses food intake and increases energy expenditure and prevents obesity on a high fat diet. In addition, activation of ERβ affects peripheral energy and glucose homeostasis by 1) favoring pancreatic β-cell survival and function by preventing pro-apoptotic injuries and increasing GSIS, 2) preventing obesity and decreasing WAT mass, 3) promoting insulin resistance in absence of ERα activation. ERα and ERβ metabolic actions on peripheral tissues result from direct activations of ERs in these tissues or from a central ER action affecting peripheral tissues via the autonomous system CNS ERs.




I'll post the DHT target tissues illustration , (way cool)
_________________

And on ther hand---from the study you listed:

Differential effects of exogenous androgen and an androgen receptor antagonist in the peri- and postpubertal murine mammary gland.
Conclusion-
Our findings indicate that androgen signaling influences development and structure of the adult mammary gland and that homeostasis between estrogen and androgen signaling in mature glands is critical to constrain the proliferative effects of estradiol.
http://www.ncbi.nlm.nih.gov/pubmed/21846805#

This is really intriguing (specifically) this statement.

flutamide treatment from 12-21 wk increased ductal branching (P = 0.004)

Which I gather (flutamide, AR) does have an impact on side branching.

thank you Lotus, I'm ready to go. Happy me!
yep you gave to a scientist a good homework

Did i?..... cool, I thought I might have insulted you lol.

How come, am I the only one? Where are all the others? There is a lot of people here.

Don't know....but I'm glad you're here. I have all kinds of crazy ideas and only myself to entertain them, lmao.

Anyway, you could be a scientist.

You think so?, nah....... I'm not worthy although I'd love to be one. and thank you so much for saying so.

I want to link these posts together, hopefully you'll see the importance of how fatty acids can and does have a huge impact on NBE. And considering how effective FA's are in low concentrations it's particularly appealing.


Inhibition of steroid 5 alpha-reductase by specific aliphatic unsaturated fatty acids.

Human or rat microsomal 5 alpha-reductase activity, as measured by enzymic conversion of testosterone into 5 alpha-dihydrotestosterone or by binding of a competitive inhibitor, [3H]17 beta-NN-diethulcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one ([3H]4-MA) to the reductase, is inhibited by low concentrations (less than 10 microM) of certain polyunsaturated fatty acids. The relative inhibitory potencies of unsaturated fatty acids are, in decreasing order: gamma-linolenic acid greater than cis-4,7,10,13,16,19-docosahexaenoic acid = cis-6,9,12,15-octatetraenoic acid = arachidonic acid = alpha-linolenic acid greater than linoleic acid greater than palmitoleic acid greater than oleic acid greater than myristoleic acid. Other unsaturated fatty acids such as undecylenic acid, erucic acid and nervonic acid, are inactive. The methyl esters and alcohol analogues of these compounds, glycerols, phospholipids, saturated fatty acids, retinoids and carotenes were inactive even at 0.2 mM. The results of the binding assay and the enzymic assay correlated well except for elaidic acid and linolelaidic acid, the trans isomers of oleic acid and linoleic acid respectively, which were much less active than their cis isomers in the binding assay but were as potent in the enzymic assay. gamma-Linolenic acid had no effect on the activities of two other rat liver microsomal enzymes: NADH:menadione reductase and glucuronosyl transferase. gamma-Linolenic acid, the most potent inhibitor tested, decreased the Vmax. and increased Km values of substrates, NADPH and testosterone, and promoted dissociation of [3H]4-MA from the microsomal reductase. gamma-Linolenic acid, but not the corresponding saturated fatty acid (stearic acid), inhibited the 5 alpha-reductase activity, but not the 17 beta-dehydrogenase activity, of human prostate cancer cells in culture. These results suggest that unsaturated fatty acids may play an important role in regulating androgen action in target cells.

Inhibition of steroid 5 alpha-reductase by specific aliphatic unsaturated fatty acids.
http://www.ncbi.nlm.nih.gov/pubmed/1637346

GLA- gamma-Linolenic acid (like EPO evening primrose oil),

gamma-Linolenic acid does not inhibit 17 beta HSD dehydrogenase activity, which one has yet to be identified


Btw, 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) play an important role in the regulation of steroid hormones, such as estrogens and androgens.

http://www.ncbi.nlm.nih.gov/pubmed/12570693

It was only a matter of time when this info would be found, enjoy.

Inhibition of steroid 5a-reductase by specific aliphatic unsaturated/fattyacid
http://www.ncbi.nlm.nih.gov/pmc/articles...1-0210.pdf

fatty acids could function as endogenous inhibitors of 5a-reductase


The most potent was y-Linolenic acid, GLA-aka EPO-Evening Primrose Oil.

From the first study,

Type 1 & 5 (17beta HSD) are breast growth potentiators

[pom19]

Health and Peace be with you Lotus. I'll miss you. <3 POM

[charrr]

Lotus, you are such a geeky thing! I bet you sneak back in just to check people's math and possibly save some people from hormone havoc! Eh? Yah...

[Lotus]

Lotus, you are such a geeky thing! I bet you sneak back in just to check people's math and possibly save some people from hormone havoc! Eh? Yah...

Thanks Pom and @ char (haha, physic huh?).

I'm only here to offer a new theory relating to sex hormones in GG & GM's. Instead of inhibiting Luteinizing hormone (LH), promote its action (fish oil is a good example of how, it boosts free testosterone), then, 4 hours later promote FSH (follicle stimulating hormone) by the conversion of E2. Meaning, testosterone in peripheral tissues, by way of 5 Ar and aromatase (happening in men and women via ovaries in women and testes in men). Use pro-aromatase herbs, (white peony, forskolin, IICARIN found in horny goat weed, DHEA, etc). I believe this can boost steroid synthesis to start a growth cycle.

Boost LH (fish oil supplement)
Convert FSH to E2 from Aromatse
Fast 12-14 hrs 2-3x a week
Do HIIT (high intensity interval training) 2-3x a week.

Bottom line, Estrogen production comes from Testosterone and androstenedione. Use this (T) surge to convert to E2.

[Lotus]

Here's a new pic. If I come up with any new theories I'll stop by and share with y'all, otherwise " happy growing "

[pom19]

Here's a new pic. If I come up any new theories I'll stop by and share with y'all, otherwise "happy growing.

------------------------------------------------------------
My goodness Lotus, these watermelons of yours-