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docj077 said:Bryan said:Doctor, Stephen is making a different point here and asking a completely different question. He is pointing out that in Uno's stumptailed macaque study which was referenced earlier in this thread, they found that the dermal papillae of juvenile monkeys (pre-pubertal) didn't show any sensitivity to androgens (in the sense of inhibiting the growth of co-cultured keratinocytes), whereas the dermal papillae of post-pubertal monkeys _did_ show such a growth suppression in response to androgens.
Bryan, I believe that you already know how this system works. All you have to do is look at bodybuilders. Resistance training increases testosterone and has been found to increase androgen receptor production in target tissues (I have a study that demonstrates this, by the way). The more androgens you put into the system, the higher the production of androgen receptors will become. You reach a physiological and signal threshold and once that occurs, the follicles are sensitized. This works faster in men with early-onset male pattern baldness, because the receptor allows you to reach that threshold faster.
Michael Barry's point about length of cultivation and androgen action is likely the correct answer. male pattern baldness is a process that takes years for it to realize its full disease potential. You have to upregulate a lot of genes and deposit a lot of collagen.
Ahh....I see. Your answer to the puzzle is that the frontal hair follicles of the juvenile, pre-balding stumptailed macaques DID INDEED have an intrinsic sensitivity to androgens (in the sense that they would suppress the growth of keratinocytes that were co-cultured with them), it's just that the level of androgen receptors in the hair follicles of those youthful monkeys was so low that the suppressive effect wasn't obvious to the researchers.
Doctor, the only problem I have with that is that there was no mention of any such hypothesis from Uno and his colleagues in that study. They seem to be as puzzled by that as the rest of us (other than you and, of course, Stephen Foote! :wink: ) who have discussed this aspect of the experiment from time to time. Doesn't it seem likely that someone as experienced and famous in the field of hairloss research as Hideo Uno would have suggested such an explanation, if he felt it was reasonable? What I get from the text of that study is that the levels of androgen (testosterone) that they used should have been sufficient to produce _some_ kind of a noticeable suppressive effect, even if there were lower levels of androgen receptors in the young monkeys.
BTW, how do you explain Sawaya's claim of finding an "intense upregulation" in the numbers of androgen receptors in the hair follicles of finasteride users? That would appear to contradict what you said above (greater androgenic stimulation upregulates androgen receptors). Furthermore, a separate study ("RNA-Levels of 5a-Reductase and Androgen Receptor in Human Skin, Hair Follicles and Follicle-Derived Cells", Eicheler et al, from the book "Hair Research for the Next Millenium", 1996) found that adding testosterone to cultures of human scalp hair follicle papilla cells DOWN-regulated androgen receptor RNA, which would seem to support Sawaya's findings and contradict the theory that androgens UP-regulate androgen receptors (at least specifically in human scalp hair follicles). Do you have any thoughts on all that?
And Stephen Foote, why have YOU remained silent on this? What do you think of docj's answer to the pre-pubertal macaque puzzle?