New clinical trial intended to prove the Androgenetic Alopecia theory.

[Bryan]

The reason I wrote "still up for debate"....is that I'm not sure if male pattern baldness or FPB is brought about by the negative effects of T and/or DHT on the hair follicle directly or by their damage of the other areas and systems mentioned above. Reduction of T conversion to DHT should help either way..if the effects are direct or indirect.

With all due respect to posters here who are convinced that androgens have only some indirect effect on hair follicles (Stephen Foote's idea of "contact inhibition" is probably the best example of that), I think these ideas has been pretty soundly refuted. While it's possible to continue asking questions which can't be easily answered (like why balding hair follicles just accidentally seem to be associated with areas on the scalp underneath the galea), I think these issues have been sufficiently addressed and disproved by serious medical researchers.

 

[armandein]

Exactly,..., the current theory cannot explain easily why affects only certains hairs, In common baldness the key word is the pattern, Androgenetic Alopecia=male pattern baldness. Till then, we can have different ideas.

 

[Boba155]

All I am asking for is someone to show a study that indicates androgens in the hair follicles directly influence hair growth/miniaturization .

I am worried that scalp or skull androgen activity is the real problem, stemmed from Freakout's studies posted. If androgens in the hair follicles caused miniaturization, one would expect the hairs to miniaturize no matter what scalp they were transplanted onto, but that is not the case.

I like many others believe skull expansion is complete bullshit, but you do wonder why men with that juvenile "^" hairline never lose their hair.

 

[armandein]

All I am asking for is someone to show a study that indicates androgens in the hair follicles directly influence hair growth/miniaturization .

ALL, not only the galea's hair, scalp hairs can be afected by androgens


http://www.ncbi.nlm.nih.gov/pubmed/1693 ... stractPlus
Skin Pharmacol Physiol. 2006;19(6):311-21. Epub 2006 Aug 23.
Effect of 5alpha-dihydrotestosterone and testosterone on apoptosis in human dermal papilla cells.

Winiarska A, Mandt N, Kamp H, Hossini A, Seltmann H, Zouboulis CC, Blume-Peytavi U.

Department of Dermatology and Allergy, Charité-Universitatsmedizin Berlin, Berlin, Germany.
Abstract

Pathogenetic mechanisms in androgenetic alopecia are not yet fully understood; however, it is commonly accepted that androgens like testosterone (T) and 5alpha-dihydrotestosterone (5alpha-DHT) inhibit hair follicle activity with early induction of the catagen. Thus, we investigated the influence of T and 5alpha-DHT on proliferation, cell death and bcl-2/bax expression in cultured dermal papilla cells (DPC) from nonbalding scalp regions of healthy volunteers. T and 5alpha-DHT induced apoptosis in DPC in a dose-dependent and time-related manner; in addition a necrotic effect due to T at 10(-5) M was found. Interestingly, bcl-2 protein expression was decreased in T- and 5alpha-DHT-treated cells, leading to an increase in the bax/bcl-2 ratio. In addition, T and 5alpha-DHT induced proteolytic cleavage of caspase 8 and inhibited proliferation of DPC at 10(-5) M. High concentrations of T and 5alpha-DHT were needed to induce apoptotic effects in DPC. These data suggest that DPC from nonbalding scalp regions do have the capacity to undergo apoptosis, but need a high androgen stimulus. The present study provides an interesting new pathogenetic approach in androgenetic alopecia.

PMID: 16931898 [PubMed - indexed for MEDLINE]

 

[Bryan]

All I am asking for is someone to show a study that indicates androgens in the hair follicles directly influence hair growth/miniaturization .

I am worried that scalp or skull androgen activity is the real problem, stemmed from Freakout's studies posted. If androgens in the hair follicles caused miniaturization, one would expect the hairs to miniaturize no matter what scalp they were transplanted onto, but that is not the case.

I'm not completely sure what you mean by "androgens in the hair follicles". Are you referring specifically to androgens that are generated inside the hair follicle?

By the way, there is very good reason to think that balding hair follicles WOULD miniaturize no matter what scalp they are transplanted onto. Haven't you seen the important study by Nordström that we've discussed so much on these forums?? He transplanted balding follicles from the scalp onto the arm of a young man, and they continued to go bald at about the same rate as they did when they were on his scalp!

I like many others believe skull expansion is complete bullshit, but you do wonder why men with that juvenile "^" hairline never lose their hair.

Because their hair follicles aren't very sensitive to androgens. Isn't that rather obvious? :dunno:

 

[Boba155]

Yes, Bryan, I am talking about receptors generated inside the hair follicles.

And Bryan, while Nordstrom's study is excellent, Freakout's posted studies directly contradict it. Any opinions or explanations?

By the way Bryan, do not think in any way that I am opposing you. I support you, believe me. I just want to have rock solid evidence that it is androgens in the follicle themselves that cause miniaturization.

 

[Bryan]

Yes, Bryan, I am talking about receptors generated inside the hair follicles.

You mean ANDROGENS, not RECEPTORS?

And Bryan, while Nordstrom's study is excellent, Freakout's posted studies directly contradict it. Any opinions or explanations?

What posted studies of his do you think contradict it? :dunno:

By the way Bryan, do not think in any way that I am opposing you. I support you, believe me. I just want to have rock solid evidence that it is androgens in the follicle themselves that cause miniaturization.

Where did you get that idea in the first place? It seems clear that DHT that affects hair follicles is mostly DHT produced in the hair follicles themselves, but what about other androgens like testosterone (from which DHT is made)? There's been a hint or two by hairloss researchers that hair follicles _may_ contain the metabolic machinery to produce androgens like testosterone on their own, but the degree to which they do that (if at all) remains awfully speculative. Why are YOU so interested in this issue all of a sudden, and what does it have to do with anything else that's been posted here recently? :dunno:

 

[Boba155]

Actually no, I was talking about receptors, and I'll explain why below.

Secondly, I was referring to the study that Freakout posted showing that vellus hairs when transplanted onto mice grew terminal. Nordstrom's study showed that transplanting vellus hairs grew vellus. There is a discrepancy here.

And finally, I have such a new vested interest in this because of the possibility of gene therapy for hairloss. If androgens binding to receptors inside the hair follicles is what causes miniaturization, then simply disabling the AR gene in hair follicles would cure male pattern baldness. Permanent and quite cheap too.

 

[freakout]

... up until now the only androgen receptor blockers that I was aware of were strictly for alopecia, and only topicallty administered not internally.

If it's for scalp hair it has to be administered topically.
When ingested via digestive system, the results could be unpredictable or less effective. Via transfution, it will affect all androgen receptors on all organs.

My guess is it will induce a hypotestosteromic affect. Skin will sag. Muscles will atrophy. The other concern is resistance.

 

[Bryan]

Do you happen to know levels?....not how much is made, more like site level, or local concentration in the follicle itself? :dunno:

No I don't, sorry. Even professional hairloss researchers have disagreed on levels of so-called "scalp DHT", which is why I think it's all pure speculation to wonder about specific levels of DHT inside hair follicles.

 

[Bryan]

Actually no, I was talking about receptors, and I'll explain why below.

All androgen receptors are generated inside the cells in which they appear.

Secondly, I was referring to the study that Freakout posted showing that vellus hairs when transplanted onto mice grew terminal. Nordstrom's study showed that transplanting vellus hairs grew vellus. There is a discrepancy here.

No, Nordström's study showed that transplanting balding hair follicles onto other body areas of the same balding man continued to go bald (a man that wasn't using finasteride or antiandrogens of any kind).

I don't know why the mice in the other study regrew hair so well, and neither do the researchers! In any event, it's not terribly practical or important, since it was such a contrived experiment: hair follicles from balding humans transplanted onto genetically mutated mice?? An experiment which only done just that one time, and hasn't been duplicated by anybody else? An experiment which has been CONTRADICTED by other researchers like Sintov? As I've said numerous times: it's an interesting experiment, but I don't really have any idea what to make of it.

And finally, I have such a new vested interest in this because of the possibility of gene therapy for hairloss. If androgens binding to receptors inside the hair follicles is what causes miniaturization, then simply disabling the AR gene in hair follicles would cure male pattern baldness. Permanent and quite cheap too.

You really think it would be "cheap" to find a way to safely disable the AR gene only in the scalp?

 

[Bryan]

But they should grow their hair back according to Androgenetic Alopecia! :woot:

Always remember: Hamilton found decades ago that even castration doesn't have very much of an effect at hair regrowth.

 

[Boba155]

You misunderstand Bryan. I am wondering wether it is androgens binding to the receptors inside the hair follicles is what causes miniaturization, rather than binding to AR's in close proximity to the hair follicle (which Nordstrom did say was a possibility!).

 

[Bryan]

You misunderstand Bryan. I am wondering wether it is androgens binding to the receptors inside the hair follicles is what causes miniaturization, rather than binding to AR's in close proximity to the hair follicle (which Nordstrom did say was a possibility!).

Oh, I think that's a pretty trivial question.

 

[Boba155]

Oh really?

Prove it.

 

[Bryan]

I can't prove that, but androgens do have the same effects on hair follicles in vitro that they do in vivo. I don't spend even a moment at night lying in bed, wondering if maybe some other androgen receptors (besides the ones inside hair follicles) are what really cause balding.

 

[Boba155]

Well you should. If it's the ARs in the hair follicles themselves, then we can cure it with gene therapy.

If not, we are sh*t out of luck, because disabling ARs systemically would literally be castration.

 

[Bryan]

Well you should. If it's the ARs in the hair follicles themselves, then we can cure it with gene therapy.

If not, we are sh*t out of luck, because disabling ARs systemically would literally be castration.

Judging by your previous post on that issue, what makes you think it would be so easy or safe (or "cheap") to alter the production (or structure) of androgen receptors inside hair follicles only? :dunno:

 

[Boba155]

Bryan, I working a lab. Believe me, it would be very easy. Safe? Perhaps, perhaps not.

 

[Bryan]

Considering that we already have examples of locally-effective antiandrogens and 5a-reductase inhibitors to help fight male pattern baldness in scalp hair follicles, THAT would appear to be currently the better and safer way to do it, rather than take big chances with gene therapy on the androgen receptor. If something goes wrong with that last one, it could have scary results.