What Is Up With This Old Study. 5ar1 Active In Hair Follicle

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https://www.ncbi.nlm.nih.gov/pubmed/11962492

Type-1 steroid 5 alpha-reductase is functionally active in the hair follicle as evidenced by new selective inhibitors of either type-1 or type-2 human steroid 5 alpha-reductase.
Gerst C1, Dalko M, Pichaud P, Galey JB, Buan B, Bernard BA.
Author information

Abstract
Steroid 5 alpha-reductase catalyzes the reduction of testosterone (T) into the very potent androgen dihydrotestosterone (DHT). The different tissue expression patterns of the two isoforms of 5 alpha-reductase, namely type-1 and type-2 5 alpha-reductase (5 alpha-R1 and 5 alpha-R2, respectively), have prompted studies directed towards the synthesis of selective 5 alpha-R1 or 5 alpha-R2 inhibitors. In this present work, we have performed a structure/activity study on the inhibitory potential of indole carboxylic acids against hair follicle 5 alpha-reductase activity. We have demonstrated that this class of molecules were potent inhibitors of either 5 alpha-R1 or 5 alpha-R2 or both depending on (i) substituents in positions 4, 5 or 6 and (ii) the presence of a free carboxylic group. We have also found that only 5 alpha-R1 or 5 alpha-R1/R2 inhibitors were able to inhibit 5 alpha-reductase activity in plucked hairs from female volunteers or in freshly isolated female hair follicles, selective 5 alpha-R2 inhibitors being inactive.




How does this make sense? Only type II is suppose to be in the hair follicle. Are they not talking about dermal papilla in the above study?

 

[dm900]

I mean they should be, this is a little beyond me. I still don't believe type 1 DHT has a role in the initiation of Androgenetic Alopecia, although it might contribute to it once it has started.

 

[Michael1986]

It has been known for a long time that both types of 5ar are present in the hair follicles. The following study found that 5ar1 is present in all regions of the hair follicles, while 5ar2 is only present in some regions: https://academic.oup.com/jcem/article/86/6/2875/2849389.
The logical conclusion that can be drawn from this study is that 5ar1 must play some sort of a role in male pattern baldness seeing as it is present in all regions of the hair follicles including the dermal papillae.

The greater effectiveness of dutasteride over finasteride as a male pattern baldness treatment is likely to be due to both its more complete inhibition of 5ar2 as well as its additional partial inhibition of 5ar1.

 

[Feelsbadman.jpg]

It has been known for a long time that both types of 5ar are present in the hair follicles. The following study found that 5ar1 is present in all regions of the hair follicles, while 5ar2 is only present in some regions: https://academic.oup.com/jcem/article/86/6/2875/2849389.
The logical conclusion that can be drawn from this study is that 5ar1 must play some sort of a role in male pattern baldness seeing as it is present in all regions of the hair follicles including the dermal papillae.

The greater effectiveness of dutasteride over finasteride as a male pattern baldness treatment is likely to be due to both its more complete inhibition of 5ar2 as well as its additional partial inhibition of 5ar1.

Then why do psuedohermaphrodites who lack 5ar2 but not 5ar1 never experience baldness? Not even frontal recession. Also dutasteride performs similarly to finasteride, only faster.

 

[Michael1986]

Then why do psuedohermaphrodites who lack 5ar2 but not 5ar1 never experience baldness? Not even frontal recession. Also dutasteride performs similarly to finasteride, only faster.

That's a very good point to mention that the pseudohermaphrodites in the Dominican Republic did not suffer from male pattern baldness. It should be pointed out however, that they were few in number (47 I believe), and they were all related to one another and were from one small isolated village, and being from the Dominican Republic, they were of an ethnic background (which includes part Native American DNA) that is less prone to baldness than Europeans. It could be that most or all of them were not prone to male pattern baldness anyway.
It may be that if there is absolutely no 5ar2 present at all, 5ar1 on its own is too weak to trigger the chain of events that underlies male pattern baldness, but if 5ar2 is also present, the combined effect of the action of both enzymes is greater than just the effect of 5ar2 on its own. I'm not denying that 5ar2 is far more important in hair loss than 5ar1. I'm just hypothesising that 5ar1 may play a small role too, especially in view of the findings of the study I quoted above.

Dutasteride is not just faster at growing hair than finasteride. It is most certainly a more effective treatment also.

 

[Hairicane]

Dutasteride is not just faster at growing hair than finasteride. It is most certainly a more effective treatment also.

Why isn't dutasteride approved for hair loss?

 

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Why isn't dutasteride approved for hair loss?

It is in South Korea and Japan.

Probably not in the US because there is no profit in it. Propecia was first to market. Doesn't matter who has the better product always. In the trials, dutasteride showed better results but only marginally compared to finasteride. Also propecia was not a financial success. GSK went for the BPH because there is more money. Expensive phase III trials for hair loss not really worth it in the US. In Asia, hair loss makes more money I think.

 

[Feelsbadman.jpg]

That's a very good point to mention that the pseudohermaphrodites in the Dominican Republic did not suffer from male pattern baldness. It should be pointed out however, that they were few in number (47 I believe), and they were all related to one another and were from one small isolated village, and being from the Dominican Republic, they were of an ethnic background (which includes part Native American DNA) that is less prone to baldness than Europeans. It could be that most or all of them were not prone to male pattern baldness anyway.
It may be that if there is absolutely no 5ar2 present at all, 5ar1 on its own is too weak to trigger the chain of events that underlies male pattern baldness, but if 5ar2 is also present, the combined effect of the action of both enzymes is greater than just the effect of 5ar2 on its own. I'm not denying that 5ar2 is far more important in hair loss than 5ar1. I'm just hypothesising that 5ar1 may play a small role too, especially in view of the findings of the study I quoted above.

Dutasteride is not just faster at growing hair than finasteride. It is most certainly a more effective treatment also.

Actually in the studies the results are similar for 5 mg finasteride and .5 mg dutasteride if you stretch out the time frame long enough. 6 months of .5 mg dutasteride did what 5 mg of finasteride took 1 year to achieve I believe. But the results plateau as far as regrowth so in the long run, they are similar. I do believe dutasteride is far superior for maintenance though. In the 10 year finasteride study, 86% were at or above baseline. In a 10 year dutasteride study, I think it would be closer to 100%.