[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