[-Clelia-]

O.k., I am no scientist, but here is a wild thought. Could the membranes in female breast's be somewhat different than their brother's?? Maybe the xy combo chromosome double locks the male breast somehow?? Or at the least makes it less permeable to Estradol expression or straight out E in all forms?????

iaboy, I like Clelia's explaination, what's weird is that I tried to address/explain the exact cause (or, lack of cause) for why the breast growth response is individually diverse. And.....well.....you know me to go over board with info. but...here's my .02 cents worth.

hi, i think the main difference between male and female is in the AR receptor number in breast tissue. Also, hormones play another important role. What is fondamental to development are the ratios: AR/ER, androgen/estrogen. The higher are those numbers, the smaller is your breast

Out of interest, would they have been markedly different on an HRT regimen, do you think? (Not that I propose to follow one).

It's hard to say. What is interesting is when PM gets carried over to hrt from nbe. The two receptor proteins (alpha and beta) are well documented, the relationship between NBE, HRT, Breast Cancer is somewhat tied together, and explains how/why growth is mediated.

Role of receptor complexes in the extranuclear actions of estrogen receptor a in breast cancer
http://erc.endocrinology-journals.org/co...3.full.pdf


We've seen folks on hrt return to nbe, and then go back on hrt. Receptor mediated growth (or lack thereof) explains quite a bit. For instance (and this will sound crazy) you've heard the term "they have good genes, or the good genes passed on, etc etc, its quite possible and directly related to the amount of breast growth genes (per this example), imo it best describes the relationship between small breasted to large breasted women ( put men in this group too, since we have the same receptors).

I tend to look at how these proteins (enzymes) are structured, meaning what influences the binding process, e.g. protein kinase or the phosphorylation of proteins, PPK, TNF receptor family, cAMP, caveolin, with signaling proteins, G-proteins, Src-like kinases, I mean the list goes on and on.

Tap into signaling pathways (intracellular) or.... what inhibits cells migration ..... LBD (ligand binding domain) which is mediated somewhere @ 66% of ER-a domain and the doors start opening for breast growth......well....that's certainly my opinion. All the research is there, it's just interpreting into language humans can understand, easy right?.

Now Clelia is here to help interpret (lol, translate) right Clelia.

ouch..!
yes, I think, different sizes obtained with NBE can be explained:
the same followed program is good for some, and not the best for others, for physiological differences (different receptor response, different signallin pathways, different number of total hormone receptor, and different amount of circulating hormones)

[-Clelia-]

mmh... i never liked soy, imo is not a healthy food. Maybe there is some advantage for some people (after menopause, or before to low breast cancer risk), but I dont like the way it interferes in the brain.
That's just my opinion.
I will attach a study about food and phytoestrogen content. Soy is the highest source of genistein and daidzein.
With your findings, you should be carefull for prostate risk. Because those compounds exert antiestrogenic effect in 2 ways: occupying er receptor, giving weak or no response, and also 3b-diol is inhibited. Now i see how asian women (high soy consumer) have the smallest breast average in the world, and lower cancer risk in young women

ok...I made a wrong hypothesis. i just found that isoflavones from soy low the prostate cancer (PC) risk. But now i remember of some post linking PC to high estrogen activity (but somewhere you can read also the androgen high activity implied in PC...). I will report the links in few hours. I found something also on phytoest. on brain activity... That i don't like. Why are we sooo complicated?

[Lotus]

mmh... i never liked soy, imo is not a healthy food. Maybe there is some advantage for some people (after menopause, or before to low breast cancer risk), but I dont like the way it interferes in the brain.
That's just my opinion.
I will attach a study about food and phytoestrogen content. Soy is the highest source of genistein and daidzein.
With your findings, you should be carefull for prostate risk. Because those compounds exert antiestrogenic effect in 2 ways: occupying er receptor, giving weak or no response, and also 3b-diol is inhibited. Now i see how asian women (high soy consumer) have the smallest breast average in the world, and lower cancer risk in young women

ok...I made a wrong hypothesis. i just found that isoflavones from soy low the prostate cancer (PC) risk. But now i remember of some post linking PC to high estrogen activity (but somewhere you can read also the androgen high activity implied in PC...). I will report the links in few hours. I found something also on phytoest. on brain activity... That i don't like. Why are we sooo complicated?

Hi Clelia,

I've seen soy reports on oriental men, at which time it showed positive results. And I thought to myself duh!!, their consumption of soy compared to western world will effect outcome. But I'm remember seeing a western study that basically revealed lower sperm motility from soy supplementation.

[-Clelia-]

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

[Lotus]

In this study they point out DHT is both metabolized in blood and peripheral tissue, and that 3a-doil is reversible by reduction/oxidation, which we already knew it wasn't reversible by 5-ar. It's a great study, I wish they went further to include aromatase, but......blood conversion is stated at 4%


Dihydrotestosterone is a peripheral paracrine hormone
http://onlinelibrary.wiley.com/store/10.1002/j.1939-4640.1992.tb01621.x/asset/j.1939-4640.1992.tb01621.x.pdf?v=1&t=i7yzh12e&s=b7d3003cefc60b1c1bdf3dfaa8caf08a321bf736

Oh hi Clelia, I just see you posted, I'll have to check it all out, thanks.

[-Clelia-]

"What's also interesting is how upon excertion steroids are water soluble"-->
mmh... why do you want to know that? for transport?

Yes exactly, (for transport), ion channels are the access of cell diffusion correct?, assuming carrier proteins are the vehicles to mitochondria, what keeps the channels open long enough expression?, I see its from 1/100 hundredth to 1/1000 thousands of seconds, could this explain partial binding?.

I think that there is no necessity of a ion channel for the access of steroids in the cell. They should simply cross the membranes by diffusion:

"After secretion by the endocrine glands, the hormones are transported to the target tissues via the blood, where their major fraction is bound to the serum proteins β-globulin and albumin. According to the genomic mechanism, the lipophilic character of the hormones enables them to dissociate spontaneously from the carriers and enter the target cell by transbilayer passive diffusion. Inside the cell, the hormones bind to intracellular receptors that shuttle between the nucleus and the cytoplasm in an inactive state (Lundberg, 1979). Binding to the hormones induces conformational changes and reorganization to active hormone-receptor complexes (Guiochon-Mantel et al., 1996). Subsequently, the complexes migrate to the nucleus, where they bind to hormone-responsive elements on the DNA and regulate synthesis of new proteins that are required for the hormone's action (Chen and Farese, 1999; Beato and Klug, 2000)."

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1304487/

[-Clelia-]

I think that DHT is not converted to the "estrogen-like metabolite" in the breast, at least not in the same amount as it is in the prostate.

a hypothetical about DHT, (but first), for the longest time I thought DHT had no usable purpose in terms of breast growth. Now, we discover it has a back door useable metabolite in the prostate and Sertoli cells. So....then, is it yet to be discovered that DHT in breast tissue "can" in fact....have the usable ER-beta metabolite??.....that is my hypothetical, I see you think perhaps the same is true.

We've just opened a whole can of worms.......imo it's the gummi type (yum yum).

yes it could be... if you can convert the majority of DHT, in breast tissue, it could be a way for NBE. But i think that this method is quite difficoult to obtain... you should enhance the enzyme that give you 3b-diol, but honestly I dont know how this could be possible.

sorry about that :-/ i'm not mothertongue

No problem, Io capisco perfettamente,

Sorry, but I've have 4-5 research papers just related to our discussion that I'll share next.

nice one, capisci perfettamente
don't worry about papers, it's hard but fair enough

[-Clelia-]

hi Lotus! we are here now togheter

i'll reply soon at your message

[Lotus]

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

Absolutely, it benefits NBE by reducing DHT and up-regulates estrogen receptors. Here's some interesting info on how estrogens behave (mayo clinic), it's been stated before that PM behave's like E1 (estrone). I've highlighted the points of interest. For example, E1 plays a role in peripheral aromatization of androstenedione (that's through the A4 pathway), IMO, it's a back door growth opportunity. But circulating E2 is the most bio-active (free) estrogen, in other words, the strongest estrogen. Phytoestrogens don't produce estrogens as we know, but they up-regulate estrogen receptors, that's where E2 (the body's own natural estrogen, not the pharma kind, that's a different topic altogether, interact with receptors and activate growth), Hopefully.

But.....if you don't reduce DHT (as we know) breast growth is very limited, that's the bottom line.....

Estrogens are involved in development and maintenance of the female phenotype, germ cell maturation, and pregnancy. They also are important for many other, nongender-specific processes, including growth, nervous system maturation, bone metabolism/remodeling, and endothelial responsiveness. The 2 major biologically active estrogens in nonpregnant humans are estrone (E1) and estradiol (E2). A third bioactive estrogen, estriol (E3), is the main pregnancy estrogen, but plays no significant role in nonpregnant women or men.

E2 is produced primarily in ovaries and testes by aromatization of testosterone. Small amounts are produced in the adrenal glands and some peripheral tissues, most notably fat. By contrast, most of the circulating E1 is derived from peripheral aromatization of androstenedione (mainly adrenal). E2 and E1 can be converted into each other, and both can be inactivated via hydroxylation and conjugation. E2 demonstrates 1.25-5 times the biological potency of E1. E2 circulates at 1.5-4 times the concentration of E1 in premenopausal, nonpregnant women. E2 levels in men and postmenopausal women are much lower than in nonpregnant women, while E1 levels differ less, resulting in a reversal of the premenopausal E2:E1 ratio. E2 levels in premenopausal women fluctuate during the menstrual cycle. They are lowest during the early follicular phase. E2 levels then rise gradually until 2 to 3 days before ovulation, at which stage they start to increase much more rapidly and peak just before the ovulation-inducing luteinizing hormone/follicle stimulating hormone surge at 5 to 10 times the early follicular levels. This is followed by a modest decline during the ovulatory phase. E2 levels then increase again gradually until the midpoint of the luteal phase and thereafter decline to trough, early follicular levels.

Measurement of serum E2 forms an integral part of the assessment of reproductive function in females, including assessment of infertility, oligo-amenorrhea and menopausal status. In addition, it is widely used for monitoring ovulation induction, as well as during preparation for in vitro fertilization. For these applications E2 measurements with modestly sensitive assays suffice. However, extra sensitive E2 assays or simultaneous measurement of E1, or both are needed in a number of other clinical situations. These include inborn errors of sex steroid metabolism, disorders of puberty, estrogen deficiency in men, fracture risk assessment in menopausal women, and increasingly, therapeutic drug monitoring, either in the context of low-dose female hormone replacement therapy or antiestrogen treatment.

http://www.mayomedicallaboratories.com/t...tive/81418

Steroid Pathway
http://www.mayomedicallaboratories.com/i...thways.pdf

[Lotus]

Here's some interesting research about Finasteride. The ironic part was that I found the commentary after this particular statement peaked my interest after investigating the study.

"When DHT formation is inhibited, the aromatization pathway of T to estradiol will prevail and induce a pronounced down-regulation of AR mRNA levels."

Testosterone down-regulates the levels of androgen receptor mRNA in smooth muscle cells from the rat corpora cavernosa via aromatization to estrogens.

Lin MC, Rajfer J, Swerdloff RS, Gonzalez-Cadavid NF.

Department of Surgery, UCLA School of Medicine, Torrance 90509.

Androgens down-regulate the levels of androgen receptors (AR) and AR mRNA in the penis and prostate of castrated rats, and are assumed to cause their decrease during sexual maturation in the penile smooth muscle of intact rats. In order to determine whether these effects occur directly at the target cell level, and to what extent they are due to testosterone (T) or to their metabolites, we have measured AR mRNA in cultures of smooth muscle cells from the adult rat corpora cavernosa treated in vitro with sex steroids. T at high concentrations (100 nM) acted like dihydrotestosterone (DHT) in increasing moderately the levels of AR mRNA in both proliferating and contact-inhibited cells. However, when conversion of T to DHT was blocked by the 5-alpha reductase inhibitor finasteride, the levels of AR mRNA were considerably down-regulated by T (10-500 nM), particularly in the contact-inhibited cells. Finasteride by itself was inactive. These effects in both types of cultures were inhibited by platelet derived growth factor (PDGF) (20 ng/ml), a growth factor that up-regulates AR mRNA levels, and by fadrozole (100 nM), an aromatase inhibitor of the T/estrogen conversion. Estradiol (50 nM) was even more potent than T in decreasing AR mRNA levels. With the exception of PDGF none of the treatments affected significantly cell growth, as measured by DNA synthesis and content. Our results indicate that it is possible to modulate in vitro AR mRNA levels in the penile smooth muscle cells, and that under normal conditions DHT and T act as moderate up-regulators. When DHT formation is inhibited, the aromatization pathway of T to estradiol will prevail and induce a pronounced down-regulation of AR mRNA levels. We assume that the in vivo AR down-regulation in the penile smooth muscle by androgens is an indirect effect mediated by a paracrine or endocrine mechanism elicited in another tissue.
PMID: 8499343 [PubMed - indexed for MEDLINE]

-Using finasteride will block conversion of testosterone to DHT
-Using finasteride will increase testosterone(temporary I believe) and estradiol levels
-increase in Estradiol and Testosterone(?) down regulate AR mRNA
-the low DHT level caused by using finasteride, which blocks the conversion of testosterone to DHT, will prevent the increase of AR mRNA in both proliferating and contact-inhibited cells.

So there are some problems with finasteride:

1)low DHT which prevents the increase AR mRNA due to DHT. Does this mean that androgen receptors can't increase, that DHT can't bind to AR?

2)high estradiol due to testosterone not being converted to DHT because of finasteride, but being aromitized to estradiol which down regulates AR mRNA. What does this mean exactly? Less androgen receptors?

3)finasteride blocks conversion of testosterone to DHT. DHT is important for maintaining NO(nitric oxide/vasodilation if I am correct) activity in the penile corpus cavernosum.

Furthermore I remember reading somewhere that DHT is also antiestrogenic. DHT can compete with estrogen for the same receptor. Also that the ratio of androgens to estrogen is very important.

So by using finasteride which blocks conversion of T to DHT which makes estradiol levels increase we are changing the ratio of androgens to estrogen causing gynecomastia.

http://www.hairlosstalk.com/interact/sho...and-Dr-Lin

I like the lively conversations from the hair-loss forum