[Lotus]

Theory: Deny dht's ability to bind with androgen receptors and imagine the possibilities. *

If you took away 5-AR from these tissues and blocked the formation of DHT, then you would see some dramatic changes in physiology.

*Androgen receptor or estrogen receptor-beta blockade alters DHEA-, DHT-, and E(2)-induced proliferation and PSA production in human prostate cancer cells.

These findings support involvement of both AR and ERbeta in mediating DHEA-, DHT-, and E(2)-induced PSA expression in prostate cancer cells.
http://www.ncbi.nlm.nih.gov/pubmed/17503469

Ok, exactly how then?, the next steps are a new approach (new for NBE) and won't make sense at this point, but it will going forward.

Human type 3 3alpha-hydroxysteroid dehydrogenase (aldo-keto reductase 1C2) and androgen metabolism in prostate cells.
In prostate cells AKR1C2 acts as a 3-ketosteroid reductase to eliminate 5alpha-DHT and prevents activation of the androgen receptor. AKR1C2 does not act as an oxidase due to either potent product inhibition by NADPH or because it cannot surmount the oxidative 17beta-HSD present. Neither AKR1C2, retinol dehydrogenase/3alpha-HSD nor 11-cis-retinol dehydrogenase is a source of 5alpha-DHT in PC-3 cells.
http://www.ncbi.nlm.nih.gov/pubmed/12810547

Androgen inactivation and steroid-converting enzyme expression in abdominal adipose tissue in men.
In conclusion, androgen inactivation was detected in abdominal adipose tissue in men, with higher 3alpha/beta-HSD activity in the s.c. versus Om depot. Higher Om 5alpha-DHT inactivation rates were found in obese compared with lean men. Further studies are required to elucidate whether local androgen inactivation in abdominal adipose tissue is involved in the modulation of adipocyte metabolism and regional fat distribution in men.
http://www.ncbi.nlm.nih.gov/pubmed/17170221

Androgen metabolism in adipose tissue: recent advances.
We speculate that glucocorticoid-induced androgen inactivation could locally decrease the exposure of adipose cells to active androgens and partially remove their inhibitory effect on adipogenesis. We hypothesize that body fat distribution patterns likely emerge from the local adipose tissue balance between active androgens and glucocorticoids in each fat compartment.
http://www.ncbi.nlm.nih.gov/pubmed/19022338

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Adipose tissue intracrinology: potential importance of local androgen/estrogen metabolism in the regulation of adiposity.

The present article summarizes some of the studies available on steroid hormone conversion through the specific expression of steroidogenic enzymes in adipose tissue (adipose tissue intracrinology) and discusses the potential impact of local adipose tissue steroid metabolism on the regulation of adipocyte function and other metabolic parameters. Several studies have demonstrated significant steroid hormone uptake and conversion by adipose tissues from various body sites and in various cell fractions. Activities and/or mRNAs of aromatase, 3beta-hydroxysteroid dehydrogenase (HSD), 3alpha-HSD, 11beta-HSD, 17beta-HSD, 7alpha-hydroxylase, 17alpha-hydroxylase, 5alpha-reductase and UDP-glucuronosyltransferase 2B15 have been detected in adipose tissue or adipose cells. These studies have demonstrated potentially important roles for these enzymes in obesity, central fat accumulation, and the metabolic syndrome. Future studies on adipose tissue intracrinology will contribute further to our understanding of steroid action in adipocytes.

http://www.ncbi.nlm.nih.gov/pubmed/12660892


Pre-receptor regulation of the androgen receptor.

The human androgen receptor (AR) is a ligand-activated nuclear transcription factor and mediates the induction of genes involved in the development of the male phenotype and male secondary sex characteristics, as well as the normal and abnormal growth of the prostate. We have identified the pair of hydroxysteroid dehydrogenases (HSDs) that regulate ligand access to the AR in human prostate. We find that type 3 3alpha-HSD (aldo-keto reductase (AKR)1C2) catalyzes the NADPH dependent reduction of the potent androgen 5alpha-dihydrotestosterone (5alpha-DHT) to yield the inactive androgen 3alpha-androstanediol (3alpha-diol). We also find that RoDH like 3alpha-HSD (RL-HSD) catalyzes the NAD(+) dependent oxidation of 3alpha-diol to yield 5alpha-DHT. Together these enzymes are involved in the pre-receptor regulation of androgen action. Inhibition of AKR1C2 would be desirable in cases of androgen insufficiency and inhibition of RL-HSD might be desirable in benign prostatic hyperplasia.

http://www.ncbi.nlm.nih.gov/pubmed/18060684





   

Sources of testosterone and 3α-androstanediol in adult male. Adult male (A) and andropause (B) The solid box shows steroidogenesis in Leydig cells, and the dotted-box shows steroidogenesis in the adrenal gland. The pathway in gray shows a backdoor pathway to 5α-DHT via 3α-diol which does not involve the intermediates Δ4-androstene-3,17-dione or testosterone. Enzymes involved in the individual steps are italicized.

http://www.ncbi.nlm.nih.gov/pmc/?term=18060684%5BPMID%5D&report=imagesdocsum