you can't necessarily extrapolate results in rats to humans. First, finasteride inhibits *both* types of 5AR, I and II, in rats. In humans it's basically selective for type II.
Yes, Finasteride inhibits both isozymes equally in rat -- however, 5AR2 is specifically found in genital tissues in both human AND rodent models, thus making extrapolations is possible when it comes to the drug's effects on inhibition within those tissues.
Leading researchers have already confirmed this exact point, using data from animal models as the basis for explaining negative effects of the drug in humans, such as ED:
The Effect of 5 -Reductase Inhibitors on Erectile Function
http://www.andrologyjournal.org/cgi/con ... l/29/5/514
Further evaluation of the role of DHT in the penis has been done at the penile morphologic level. Shen et al (2000) investigated the ultrastructural changes of the penile corpus cavernosum and tunica albuginea in rats representing 3 groups: sham control, castrated, and treated with finasteride. Four weeks later, blood samples were obtained for the determination of serum T and DHT levels, and penile tissues were taken for scanning electron microscopy. The T and DHT levels in castrated rats and the DHT level in finasteride-treated groups were significantly lower than those in the control group. In the castrated animals, there was a high degree of fibrosis in the corpus cavernosum with irregularly arranged collagenous fibers and a marked decrease in smooth muscle fibers, while
in the DHT-inhibited group (finasteride-treated), the corpus cavernosum comprised a substantial amount of thick and irregularly arranged collagenous fibers, but the degree of fibrosis was less than that of the castration group (Shen et al, 2000).
This work suggests that because finasteride inhibits the action of DHT but not T on the corporal cavernosal tissue, the degree of fibrosis was less in the DHT-inhibited group than in the castration group. In the castration group, the thickness of tunica albuginea decreased significantly and the elastic fibers were mostly supplanted by collagenous fibers, and
in the DHT-inhibited group, the elastic fibers were replaced by disorganized and thick collagenous fibers.
Since the tunica albuginea plays a major role in the erectile mechanism of the penis, the latter results offer an explanation for the presentation of ED in patients treated with 5ARIs.
On the final question of the 'other functions' of 5AR/DHT, I'm reassured by the fact that men with a natural 5AR deficiency seem to get along fine apart from their lack of genital development
Being born as a pseudohermaphrodite is completely different compared to taking a fully functional man with a working 5AR2 enzyme, and then transforming his hormonal profile to match that of a genetically deficient 5AR2 mutant via Finasteride. They (5AR2 deficient pseudohermaphrodites) are freaks of nature -- an exception, NOT the rule -- especially considering 99.9% of the world's population has a functional 5AR2 enzyme.
This enzyme was put in our bodies for a number of reasons to support numerous critical functions, as has been alluded to in previous posts in this thread... and its not simply to make you "go bald". Additionally, 5AR2 pseudohermaphrodites may have other biological adaptations which have allowed them to appear to function "normally" without a 5AR2 enzyme (Bryan of course will disagree).
As for wether they are "healthy" or not, or lead full lifespans without succumbing to disorders as a result of being born without functional 5AR2 -- not sure if they've been followed for their entire lifespan, as I haven't come across any specific studies on this. Perhaps other posters have studies and can provide links.
For example, have any studies been done on anxiety and depression (unlisted side effects linked to inhibition of 5AR activity, ie decreased Allopregnanolone and THDOC, neurosteroids which can no longer act on GABA-A receptors in the brain) in such pseudohermaphrodites? Not to my knowledge... and just because these conditions haven't been studied in this target group, doesn't mean this is not a potential outcome of being 5AR2 deficient.
Then again, since they never had a functional 5AR2 enzyme in the first place, its possible their biological pathways/functioning, particularly in the spinal cord, is different vs men with functional 5AR2. In fact, there was a lengthy discussion from the poster "Alex Miller" about the potential implications of inhibiting 5AR2 when it comes to neurological damage, and how normal men are NOT the same as genetically deficient 5AR2 pseudohermaphrodites. Read it here:
http://www.hairlosshelp.com/forums/mess ... erthread=y
People are free to make up their own minds, of course. But the information presented is certainly worth considering. Also, I find it interesting that Bryan, who is one of the most knowlegeable posters on these sites, refuses to take Finasteride himself, for whatever reason. Interesting to note.
