Hi everyone. This is probably a dumb question. But I've read a number of times that 5AR-I is less of a culprit in male pattern baldness than 5AR-II. I'm not sure that I understand this. If both 5AR-I and II bind with testosterone to form DHT, which then binds to hair follicles and triggers an autoimmune response, why would 5AR-I be less of a culprit than Type II? Is there something different about the DHT formed with Type I? Thanks.
Question on culprit: 5AR-I or II?
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socks
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Bryan said:
Exactly. And to Elaborate just a tad further it is important to understand that DHT is formed inside cells. The DHT that is responsible for causing male pattern baldness is formed inside the hair follicle cells. As Bryan said, the Type II 5ar is the enzyme that is exclusively or nearly exclusively found in the hair follicle cells.
Some people (including myself) once thought that DHT could travel from place to place and infuse into the hair follicles cells causing damage. The truth is, the damage is caused from within the hair follicle cells by the hair follicle's cell internal DHT production. DHT outside the hair follicle cell is irrelevant.
Pirate Commander F.B.
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The butler did it.
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global said:
It _can_ do that, but there are some lines of evidence suggesting that it's the internally produced DHT which is mainly responsible for its effects in various body locations like hair follicles, sebaceous glands, the prostate, etc.
Please be very careful to notice that I am definitely NOT saying that serum DHT has no effect at all, just that the great majority of the effect is from "locally produced" DHT.
Bryan
socks
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smudge said:
From talking to Bryan, it is my understanding that little DHT infuses in and out of the hair cell follicles.
global said:
Here is a exact quote from Bryan on the subject:
"Some of it (a minority) diffuses out of the cells and enters the bloodstream, where it _may_ possibly reach other parts of the body. However, I think the available evidence indicates that such an "endocrine" role for DHT is a relatively minor one. The main effect of DHT takes place in the cells where it's actually produced. The concentration of DHT inside such cells is undoubtedly much higher than the concentration in the bloodstream, because only a minority of DHT diffuses out of the cells, and it's metabolized and excreted rather quickly once it hits the bloodstream."
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Here's an interesting tidbit of information from "A model for the turnover of dihydrotestosterone in the presence of the irreversible 5a-reductase inhibitors GI198745 and finasteride", Gisleskog et al, Clin Pharmacol Ther 1998;64: 636-47:
"...The elimination rate of DHT, k(OUT), was relatively high, corresponding to an elimination half-life of about 2 hours."
They were referring to serum levels of DHT in that statement, of course. It's eliminated fairly darned fast: if you could suddenly inhibit all the 5a-reductase throughout the body, half of the DHT already in the blood would be gone in only a couple of hours. And I read in another study (sorry, I don't remember the source) that the majority of the DHT molecules that are generated inside cells actually bind with androgen receptors and get translocated to the nucleus where they cause their androgenic effect. That strongly suggests to me that the concentration of DHT inside cells is considerably higher than what's in the blood serum itself; therefore, naturally existing levels of DHT in the blood must not have all that much of an endocrine effect, in my opinion.
Bryan
"...The elimination rate of DHT, k(OUT), was relatively high, corresponding to an elimination half-life of about 2 hours."
They were referring to serum levels of DHT in that statement, of course. It's eliminated fairly darned fast: if you could suddenly inhibit all the 5a-reductase throughout the body, half of the DHT already in the blood would be gone in only a couple of hours. And I read in another study (sorry, I don't remember the source) that the majority of the DHT molecules that are generated inside cells actually bind with androgen receptors and get translocated to the nucleus where they cause their androgenic effect. That strongly suggests to me that the concentration of DHT inside cells is considerably higher than what's in the blood serum itself; therefore, naturally existing levels of DHT in the blood must not have all that much of an endocrine effect, in my opinion.
Bryan
jimmystanley
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if socks and bryan are on to something...then this definitely points to the importance of using a topical DHT inhibitor....too bad there isn't a decent one out there....soon though.