[Lotus]

The death of DHT,

dutasteride (the strongest anti-androgen) dual inhibition reduces median serum DHT levels by 90% at 2 weeks and 93% at 2 years.

This is why breast growth takes a while, include feminaztion in the statement. So, a little help from the studio audience please.


If males produce 3mg to 10mg of Testosterone daily and 4% gets converted to DHT, how much anti-androgens are needed to give DHT a proper burial?, (I think of it as the NBE therapeutic edge)


????..... Give it your best shot, no one answer is a wrong answer.

Wouldn't it depend on the effectiveness of the particular anti-androgen(s) in each given individual? If John has a higher tolerance than Tim, then John would need more.

True froger it would, I suppose that's why the big variance. The other variable is the active part (free state) the concentration is. I'm looking at if the strongest AA out there (dutas) is eventually up to 93% after 2 years we're certainly leaving out of DHT on the table then we know about. In other words, most labs won't test for DHT or free T unless directed because of the expense (insurance). But let's say the most aggressive Hrt plan using dutas is 2mg, and let's throw in Finasteride For the heck of it, 6 mg in an aggressive hrt plan, which Finasteride gets reported @ DHT inhibition of 90 to 95%, but we'll say 90% for now. If we're at the top end (10 mg) were 4 mg shy of that therapeutic threshold to bury DHT. Dutas at 93% because of its strength (3% more) I'm gonna say 2mg shy. Sorry my math sucks, but 4% (DHT) of 10 mg of T is .4 mg but.....DHT is 30 times stronger than T, so we'll need 28mg more of Finasteride and 20-22mg of dutas. Did I loose yah?, I wouldn't be surprised lol.

So, no answer seems unreasonable to me, or better math skills.

[froger]

DHT is an interesting subject for me because it seems to be particularly stubborn.

[Lotus]

DHT is an interesting subject for me because it seems to be particularly stubborn.

It's the bottom line in NBE growth prevention, here's a quote from a recent 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."

I mean it can't be any clearer, DHT is a major pain.

[pom19]

Lotus, I thank you one more time for your research. <3 POM

[Lotus]

There's another way to stop DHT, but it's quite complicated, but it's canceling or denying its pathway through the use of another enzyme called the "Human type 3 3alpha-hydroxysteroid dehydrogenase" or (AKR1C2 aldo-keto reductase 1C2) HSD type 3, and that's in androgen metabolism in prostate cells.

Fancy way of saying this pathway can actually turn DHT into and estrogen metabolite in estrogen receptor beta ER-beta. This wasn't known, probably still not, but it's least it could be a potential new action, but that info was posted in the Anti-Androgen section sometime ago, very complicated stuff.

Oh thanks POM, I appreciate that.

[pom19]

There's another way to stop DHT, but it's quite complicated, but it's canceling or denying its pathway through the use of another enzyme called the "Human type 3 3alpha-hydroxysteroid dehydrogenase" or (AKR1C2 aldo-keto reductase 1C2) HSD type 3, and that's in androgen metabolism in prostate cells.

Fancy way of saying this pathway can actually turn DHT into and estrogen metabolite in estrogen receptor beta ER-beta. This wasn't known, probably still not, but it's least it could be a potential new action, but that info was posted in the Anti-Androgen section sometime ago, very complicated stuff.

Oh thanks POM, I appreciate that.

================================
Lotus, please, elaborate on this one. Thanks, POM

[Lotus]

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.

[pom19]

Does prostate produce cortisteriods?

[Lotus]

Does prostate produce cortisteriods?

Great question Pom, the adrenals produce glucocorticoids from the HPA (pituitary) axis, if that's what you mean. I did say complicated right? Lol. But this action itself isn't significant enough to flip the switch of without outside (pharma) help.

There is a hrt therapy (I forgot who, sorry), that uses another process that simply bypasses all (most) of androgen production -gonadotropin-releasing hormone analogue (and I will let wiki explain this one lol)
http://wikipedia.org/wiki/Gonadotropin-r...e_analogue

A gonadotropin-releasing hormone analogue (GnRH analogue or analog), also known as a luteinizing hormone releasing hormone agonist (LHRH agonist) or LHRH analogue is a synthetic peptide drug modeled after the human hypothalamic gonadotropin-releasing hormone (GnRH). A GnRH analogue is designed to interact with the GnRH receptorand modify the release of pituitary gonadotropins FSH and LH for therapeutic purposes. Shortly after the discovery of GnRH by Nobel laureates Guillemin and Schally researchers tried to modify the GnRH decapeptide with the intent to synthesize stimulating and blocking variants.

Hormones share cholesterol as a common precursor. In consequence, the first step in steroidogenesis is cholesterol uptake or synthesis. Cells that produce steroid hormones provide themselves with cholesterol in various ways. Their main source is dietary cholesterol transported in the blood as LDL, which enters the cells through receptor-mediated endocytosis, although endogenous synthesis in the endoplasmic reticulum is sufficient when LDL levels are abnormally low as represented in people with abetalipoproteinemia (a genetic disorder of intestinal lipid absorption).[3] In lysosomes, cholesterol is separated from the proteic component of LDL and then stored within cell membranes or bound with proteins.[26]

The initial part of conversion of cholesterol into steroid hormones involves a number of enzymes of the cytochrome P450 family that are located in the inner membrane of mitochondria. Transport of cholesterol from the outer to the inner membrane is facilitated by steroidogenic acute regulatory protein (StAR) and is the rate-limiting step of steroid synthesis.[26] The functional zonation of the adrenal cortex is determined by the presence of distinct enzymes in each particular layer, explaining how the different layers produce unique hormones from a common precursor.[3]

The first enzymatic step in the production of all steroid hormones is cleavage of the cholesterol side chain, a reaction that forms pregnenolone as a product and is catalyzed by the enzyme P450scc, also known as cholesterol desmolase. After the production of pregnenolone, specific enzymes of each cortical layer further modify it. Enzymes involved in this process include both mitochondrial and cytoplasmic P450s and hydroxysteroid dehydrogenases (HSDs). Usually a number of intermediate steps in which pregnenolone is modified several times are required to form the functional hormones.[4] Enzymes that catalyze reactions in these metabolic pathways are involved in a number of endocrine diseases. For example, the most common form of congenital adrenal hyperplasia develops as a result of deficiency of 21-hydroxylase, an enzyme involved in an intermediate step of cortisol production.[27]


Glucocorticoids are under the regulatory influence of the hypothalamus-pituitary-adrenal (HPA) axis. Glucocorticoid synthesis is stimulated by adrenocorticotropic hormone (ACTH), a hormone of the anterior pituitary. In turn, production of ACTH is stimulated by the presence of corticotropin-releasing hormone (CRH), which is released by neurons of the hypothalamus. ACTH acts on the adrenal cells first by increasing the levels of StAR within the cells, and then of all steroidogenic P450 enzymes. The HPA axis is an example of a negative feedback system, in which cortisol itself acts as a direct inhibitor of both CRH and ACTH synthesis. The HPA-axis also interacts with the immune system through increased secretion of ACTH at the presence of certain molecules of the inflammatory response.[3]

Mineralocorticoid secretion is regulated mainly by the renin–angiotensin–aldosterone system (RAAS), the concentration of potassium, and ACTH to a lesser extent.[3] Sensors of blood pressure in the juxtaglomerular apparatus of the kidneys release the enzyme renin into the blood, which starts a cascade of reactions that lead to formation of angiotensin II. Angiotensin receptors in cells of the zona glomerulosa recognize the substance, and upon binding they stimulate the release of aldosterone.[28]

http://en.m.wikipedia.org/wiki/Adrenal_g...production

[pom19]

You sure answered my question. We are so fortunate to have such a researcher on our staff- <3 POM