[Lotus]

hey Lotus, dont worry, all the biochemical information is also good. Now you know how many mechanisms are involved in signal pathways I think that enhance signalling of the cells should be ok, and the fluidity of the membrane can help this. We know that a good diet can benefit these pathways for our healthy. This NBE bring you to be healtier, and well informed, and that is a nice thing. See you soon

Clelia,

Believe it or not, I was actually thinking what if ER-beta could be shifted to ER-alpha, you know.....(in layman terms).....how E2-shifts back and forth to E3 and back again (or, heterodimerize for the scientific). Well, ...wouldn't you I went looking for some research and sure enough......it's called co-synthesis of ER subtypes. But a stronger expression of co-type ER-b down-regulates ER-a expression. Which means (or explains) slow breast growth response from some phytoestrogens that have a preferential binding to ER-beta (e.g, PM, soy, gensitien).


Single-Chain Estrogen Receptors (ERs) Reveal that the ERa/b Heterodimer Emulates Functions of the ERa Dimer in Genomic Estrogen Signaling Pathways
http://www.ncbi.nlm.nih.gov/pmc/articles...9995-04.pdf


The Importance of ERα/ERβ Ratio in Breast Cancer: Mitochondrial Function and Oxidative Stress
http://cdn.intechopen.com/pdfs/23375/InT...stress.pdf

preferential binding affinity for human ER beta over ER alpha (difference up to 18-fold).

Quantitative structure-activity relationship of various endogenous estrogen metabolites for human estrogen receptor alpha and beta subtypes: Insights into the structural determinants favoring a differential subtype binding.

Abstract
To search for endogenous estrogens that may have preferential binding affinity for human estrogen receptor (ER) alpha or beta subtype and also to gain insights into the structural determinants favoring differential subtype binding, we studied the binding affinities of 74 natural or synthetic estrogens, including more than 50 steroidal analogs of estradiol-17beta (E2) and estrone (E1) for human ER alpha and ER beta. Many of the endogenous estrogen metabolites retained varying degrees of similar binding affinity for ER alpha and ER beta, but some of them retained differential binding affinity for the two subtypes. For instance, several of the D-ring metabolites, such as 16 alpha-hydroxyestradiol (estriol), 16 beta-hydroxyestradiol-17 alpha, and 16-ketoestrone, had distinct preferential binding affinity for human ER beta over ER alpha (difference up to 18-fold). Notably, although E2 has nearly the highest and equal binding affinity for ER alpha and ER beta, E1 and 2-hydroxyestrone (two quantitatively predominant endogenous estrogens in nonpregnant woman) have preferential binding affinity for ER alpha over ER beta, whereas 16 alpha-hydroxyestradiol (estriol) and other D-ring metabolites (quantitatively predominant endogenous estrogens formed during pregnancy) have preferential binding affinity for ER beta over ER alpha. Hence, facile metabolic conversion of parent hormone E2 to various metabolites under different physiological conditions may serve unique functions by providing differential activation of the ER alpha or ER beta signaling system. Lastly, our computational three-dimensional quantitative structure-activity relationship/comparative molecular field analysis of 47 steroidal estrogen analogs for human ER alpha and ER beta yielded useful information on the structural features that determine the preferential activation of the ER alpha and ER beta subtypes, which may aid in the rational design of selective ligands for each human ER subtype.
http://www.ncbi.nlm.nih.gov/pubmed/16728493

[Roserose]

There's two versions, male and female (this is the female one), (sample illustration only- not a suggested program, for illustration only).

Please Check my program (sample)


Follicular Cycle
Ainterol PM - 500mg - 2x daily
Collagen - 2x times a daily
Vit D - 2000iu -1x daily total of 2000iu
Fish oil - 1000mg 3x daily
Coconut oil 1 tbsp daily

Mid Cycle?

Luteal Cycle
Fenugreek -610mg each -3x daily
Fennel - 480mg each - 2x daily
Dong Quai -565mg -2x daily
Dandelion - 525mg -1x daily
L-Tyrosine - 500mg 1x daily

Massages/Noogleberry

Exercise

Diet/Calories Per day

Other:
___________________


Age/weight (optional)
Bust:
Overbust:
Underbust:
Goal:

Hi Lotus may i know,

Why you dont include aromatase in the sample program? Is it because its not that essential in NbE program?

[Roserose]

I have posted new reply twice but it doesnt show up here, kinda weird.

Btw Lotus may i know why you dont include aromatase in the sample program in previous page? Is it because long term use of it have bad side effects as stated above?

[Lotus]

I have posted new reply twice but it doesnt show up here, kinda weird.

Btw Lotus may i know why you dont include aromatase in the sample program in previous page? Is it because long term use of it have bad side effects as stated above?

Hi Dfleurs,

It's a fictional program, I used this an illustration of how a program would appear when we get the new section(s) up and running.

Good catch.

[Lotus]

If I do a critique in that program I'd say it has some functional aromatase with coconut oil, vit D,

Amino acids in my opinion are pro-aromatase...... Cox inhibitors too

[Roserose]

Ah i see.

So about the not taking androgen in long term kind of freak me out a bit. But its actually quite essential in NBE program right?

[Lotus]

Ah i see.

So about the not taking androgen in long term kind of freak me out a bit. But its actually quite essential in NBE program right?

That has more to do if androgens are deprived for long periods. An example would be like depleting androgens, which is impossible. An extreme example would be in castration, you'd think that would elimante androgens, but it doesn't......adrenal androgens still would exist, but.....the androgen production is minor, and technically DHT would still exist too, but overlooked.

Androgen health in women is necessary, DHT is one big obstacle too. Ovaries are the largest producer of androgens, out of that is DHEA(s) is the king. But the androstenedione pathway (of DHEA) is easier for the aromatase enzyme to E2.

[Roserose]

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

[-Clelia-]

well done Lotus, these findings about ER receptor, are very interesting! I need to study a bit, compare some studies, then I will come back here. Differences in physiology can explain different results with the same compound (ex. Genistein), also our receptors exist in "strong or weak version", then more ore less signal response to molecules. Moreover, there is 35% of population that has not the enzimatic process which converts and activate genisteine and daidzeine (they both need to cut off the glycone, to be active), this occurs in the gut. Phytoestrogen also act in opposite way, before and after menopause. I will report links later, because im using a mobile now. We need to make things clear, from the whole information. See you!

[Lotus]

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.