Minoxidil and Insulin

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M119 -- 6/5/99 updated 3/22/00

HAIR LOSS AND INSULIN

Gabe Mirkin, M.D.

Exciting new research shows that high blood levels of insulin and its growth factors may cause male pattern baldness in which men and women lose hair from the top and front of their heads, while hair on the sides of their scalp continue to grow luxuriously. A study from Harvard School of Public Health shows that men who have the highest blood levels of insulin like growth factor-1 are the ones most likely to suffer male pattern baldness. Women who have high levels of insulin (polycystic ovary syndrome) are the ones most likely to lose hair from the tops of their heads. It still is early in the research, but evidence is accumulating that male-pattern baldness may be caused by high levels of insulin that are produced by eating huge amounts of sugary and floured foods such as bakery products and pastas. We need research to show if male pattern baldness can be prevented by avoiding flour and sugar, eating fruits only with meals and taking drugs such as Glucophage, Actos and Avandia that lower insulin levels.

Signorello LB et al. Hormones and hair patterning in men: A role for insulin-like growth factor-1. Journal of the American Academy of Dermatology February, 1999;40:200-203

HGH users claim hair growth but meanwhile they experience high levels of igf-1 so maybe indirectly insulin and igf-1 reduce a hair process indirectly or over power other processes.

 

[Bryan]

OK Bryan ask your question!

It's the same question I asked you before, which you ignored the first time. Here's a copy/paste of it from my previous post:

"That's a ridiculous theory. How long do those hair follicles have to be out of a person's scalp and sitting in a petri dish before they lose their status as being 'prior contact inhibited' cells, to then be 'maintained' in that same state by androgens? I'd like to know what your answer to THAT is!"

It occurred to me after I posted it the first time that you may have ignored that question because you didn't understand its implications. I can assure you that it's a VERY serious question for you, not just a smart-alecky reply, like you probably assumed it was the first time you saw it. Please answer it very seriously.

Here's a SECOND question for you which will probably give you a little hint as to where I was going with the first one: In your estimation, what is the TGF beta-1 response to androgens in all three of the following types of hair follicles...body hair, balding scalp hair, and non-balding scalp hair?

Please answer BOTH of those questions for me!

Bryan

 

[Bryan]

I would just like to respond to a few important points Bryan.

>>Bryan wrote:
Well, Orentreich didn't actually state that they continue to miniaturize, he just stated that they "remained bald". Here's the citation: ""Autografts in Alopecia and Other Selected Dermatological Conditions", Norman Orentreich, Annals of the New York Academy of Sciences 1959; 83: 463-479.<<

Then please don't ever claim again that balding follicles "continue to bald" when transplanted into hairy areas! You have clearly mis-quoted the article, not very scientific Bryan!

How can you know that the miniaturisation continues without more comprehensive studies???

I think it's pretty darned likely that they continued to miniaturize, even if Orentreich didn't state that explicitly.

These follicles could have increased in size slightly. Not perhaps in a cosmeticaly significant way, but such an observation would be in line with modern day body hair transplantation, and might have added to further understanding!

Heheh. No, Stephen, that's highly unlikely! :wink:

When Orentreich did this research some `40' odd years ago, did he note the non long term survival of transplanted follicles in the larger grafts?

Nope. Quite to the contrary, he noted the LONG-TERM SURVIVAL of transplanted androgen-resistant hair follicles. Here's another excerpt from the study:

"For alopecia prematura [this is how they referred to androgenetic alopecia in those days] these studies would seem to indicate that the determinants of growth of strong scalp hair or of baldness lie within the local skin tissues of a full-thickness graft and suggest that the pathogenesis of common male baldness is inherent in each individual hair follicle. Probably each individual follicle is gentically predisposed to respond or not to respond to androgenic and/or other influences that inhibit its growth. This would explain the frequent clinical finding of isolated normal-growing terminal hairs in areas of male pattern baldness....This study would seem to refute theories of the pathogenesis of ordinary human baldness based solely on the 'chronic activity of the scalp muscles (via branches of the facial nerves) that lead to sheering stresses in the dermis of the scalp and consequent ischemia'....Although only 2 1/2 years have passed since the performance oof these autografts, there is evidence that local factors outside the hair follicular apparatus are not significantly related to alopecia prematura (male pattern baldness). In cases of receding hairlines in which hair-growing grafts were implanted at the periphery of the hair line, these grafts continued to grow normal hair, separated by 1 to 2 cm. from the front of the continually receding hairline..."

When he made his `donor dominance' conclusions, did he double check this conclusion by experimenting with other types of transplantation like scalp reduction?

No. I don't think anybody had thought of the idea of scalp reductions at that time.

Since these early `assumptions', a lot of desperate vunerable people, have been left scarred (Spelling OK?) by failed transplant techniques based on Orentreich's `assumption'.

HUH?? Scarring can occur INDEPENDENTLY of the issue of Orentreich's finding of donor dominance! And a lot of the other poor results from many hair transplants happens because of the poor skills of the doctors who do them. Hair transplants comprise both an artistic skill AND a science! :wink:

I've heard it all, now: you're trying to blame the sometimes poor results from some lousy hair transplant factories on the "standard theory" of hairloss!

So finally you agree with me Bryan!! Of course there are `external' factors, and androgens are a prerequisite for the process. Thats what i have been saying!

`YOU' are the one who claimed earlier that the growth process is controlled `internally' by paracrine or autocrine mechanisms. You just can't have it both ways Bryan, and you can't squirm your way out of this point!!

Uhhh....it's a matter of DEGREE, Stephen. About 90% or so of the growth process (that's just a wild guess) in balding scalp hair follicles is controlled by those paracrine or autocrine factors, and the remaining 10% is perhaps from other unknown factors. I know you just hate it when I allow a certain amount of "wiggle-room" like that when you want it to be a rigorous either/or situation, but what I said appears to be the simple truth, based on DECADES of scientific experimentation.

Bryan

 

[thin=depressed]

I think the two of you are correct to a degree.Hair loss is do to inside genetic factors as well as outside chemistry influences.

 

[S Foote.]

OK Bryan ask your question!

It's the same question I asked you before, which you ignored the first time. Here's a copy/paste of it from my previous post:

"That's a ridiculous theory. How long do those hair follicles have to be out of a person's scalp and sitting in a petri dish before they lose their status as being 'prior contact inhibited' cells, to then be 'maintained' in that same state by androgens? I'd like to know what your answer to THAT is!"

It occurred to me after I posted it the first time that you may have ignored that question because you didn't understand its implications. I can assure you that it's a VERY serious question for you, not just a smart-alecky reply, like you probably assumed it was the first time you saw it. Please answer it very seriously.

I think i understood the `implications' of your question Bryan, but if you `ARE' being serious, you are missing the point of what i have said! So i put it down to a `distraction' question.

I will concede that my term `maintaining' the effect might have been misleading, so i will answer your question as specificaly as i can. But first!

If your question is going where i think it is going, you are suggesting that once these cells are cultured in-vitro, they then `recover' from any prior contact inhibition in-vivo. So how can TGF beta 1 be `maintaining' this?

Is that your point Bryan?

Here's a SECOND question for you which will probably give you a little hint as to where I was going with the first one: In your estimation, what is the TGF beta-1 response to androgens in all three of the following types of hair follicles...body hair, balding scalp hair, and non-balding scalp hair?

Please answer BOTH of those questions for me!

As far as i can see from the studies Bryan, TGF beta 1 is largely produced in balding follicle DP cells in response to androgens, and acts to reduce the growth of the cells in-vitro.

I can find no reference to TGF beta being a factor in-vitro in respect of beard or other follicles. If you have any specific info please post it.

I will answer any points you want to make Bryan, but before i do i want you to be `specific' in your questions and criticisms Put your cards on the table Bryan, don't be shy!

S Foote.

 

[S Foote.]

I would just like to respond to a few important points Bryan.

>>Bryan wrote:
Well, Orentreich didn't actually state that they continue to miniaturize, he just stated that they "remained bald". Here's the citation: ""Autografts in Alopecia and Other Selected Dermatological Conditions", Norman Orentreich, Annals of the New York Academy of Sciences 1959; 83: 463-479.<<

Then please don't ever claim again that balding follicles "continue to bald" when transplanted into hairy areas! You have clearly mis-quoted the article, not very scientific Bryan!

How can you know that the miniaturisation continues without more comprehensive studies???

I think it's pretty darned likely that they continued to miniaturize, even if Orentreich didn't state that explicitly.

http://www.hairtransplantadviser.org/fallacies.htm[/url]

I will ask you again Bryan. Did Orentreich note this in his early research?

The answer is `NO' Bryan. Your `hero' only did half the job! You should really do some reading of the modern research, instead of just going along with the assumptions of 40-50 years ago!

So finally you agree with me Bryan!! Of course there are `external' factors, and androgens are a prerequisite for the process. Thats what i have been saying!

`YOU' are the one who claimed earlier that the growth process is controlled `internally' by paracrine or autocrine mechanisms. You just can't have it both ways Bryan, and you can't squirm your way out of this point!!

Uhhh....it's a matter of DEGREE, Stephen. About 90% or so of the growth process (that's just a wild guess) in balding scalp hair follicles is controlled by those paracrine or autocrine factors, and the remaining 10% is perhaps from other unknown factors. I know you just hate it when I allow a certain amount of "wiggle-room" like that when you want it to be a rigorous either/or situation, but what I said appears to be the simple truth, based on DECADES of scientific experimentation

NO no no Bryan, your just making it up as you go along now!

You make your own restrictions on `wiggle room' as you put it. The theory you are supporting just doesn't `HAVE' any `wriggle room'!!!

It's even in the quote you posted above about Orentreich!! Try reading the papers you claim support your arguments! Quote:

" Probably each individual follicle is gentically predisposed to respond or not to respond to androgenic and/or other influences that inhibit its growth. "

That's it in a nutshell Bryan! According to your theory, the growth response of the follicles to androgens or anything else, is inherent within the follicle! No `wriggle room' at all there Bryan. This is the whole essence of the current `donor dominance' theory you always shout about!

Only modern research is now shooting holes in your theory Bryan, and `YOU' are starting to `wriggle' 8)


S Foote.

 

[Bryan]

I will concede that my term `maintaining' the effect might have been misleading, so i will answer your question as specificaly as i can. But first!

If your question is going where i think it is going, you are suggesting that once these cells are cultured in-vitro, they then `recover' from any prior contact inhibition in-vivo. So how can TGF beta 1 be `maintaining' this?

Is that your point Bryan?

Yes, that's part of my point. In that study you quoted before which showed that contact inhibition has the same growth inhibitive effect as androgens in some particular cell line, you failed to acknowledge that the effect of the contact inhibition eventually WORE OFF in a matter of a few hours after the removal of the contact inhibition itself. If androgens cause exactly the same effect as contact inhibition in those cells, then it's unclear exactly what those researchers meant when they said that androgens "maintained" the effect of contact inhibition. I strongly suspect that it was just a very poor and confusing choice of words on the part of the person who wrote that abstract.

In any event, balding hair follicles in culture show their sensitivity to androgens for DAYS in culture with a complete absence of any contact inhibition, not for just a few HOURS like those cells did in that study. And the most important point of all is that you still haven't found any evidence that the growth inhibition of balding scalp hair follicles comes from alleged "contact inhibition", rather than the clearly demonstrated stimulation of TGF beta-1 by androgens. It's not good enough just to show that another proposed mechanism _could_ have produced a similar result, you have to provide evidence that the other proposed mechanism _did_ produce that result.

Here's a SECOND question for you which will probably give you a little hint as to where I was going with the first one: In your estimation, what is the TGF beta-1 response to androgens in all three of the following types of hair follicles...body hair, balding scalp hair, and non-balding scalp hair?

As far as i can see from the studies Bryan, TGF beta 1 is largely produced in balding follicle DP cells in response to androgens, and acts to reduce the growth of the cells in-vitro.

If you now admit that it causes such an effect in vitro, why do you find it so hard to believe that it also happens in vivo? :wink:

I can find no reference to TGF beta being a factor in-vitro in respect of beard or other follicles. If you have any specific info please post it.

I don't have any specific info on it, either. However, I find it odd that you didn't try to dismiss out of hand the idea that other hair follicles (beard or non-balding scalp hair) might have a _different_ TGF beta response to androgens than balding hair follicles! Is that a tacit admission on your part that maybe there really IS a fundamental difference in the way that balding follicles respond to androgens, compared to non-balding follicles?

I will answer any points you want to make Bryan, but before i do i want you to be `specific' in your questions and criticisms Put your cards on the table Bryan, don't be shy!

Have I ever been shy??

Bryan

 

[Bryan]

NO no no Bryan, your just making it up as you go along now!

You make your own restrictions on `wiggle room' as you put it. The theory you are supporting just doesn't `HAVE' any `wriggle room'!!!

It's even in the quote you posted above about Orentreich!! Try reading the papers you claim support your arguments! Quote:

" Probably each individual follicle is gentically predisposed to respond or not to respond to androgenic and/or other influences that inhibit its growth. "

That's it in a nutshell Bryan! According to your theory, the growth response of the follicles to androgens or anything else, is inherent within the follicle! No `wriggle room' at all there Bryan. This is the whole essence of the current `donor dominance' theory you always shout about!

ROTFLMAO, Stephen!!!

Orentreich (like other doctors and scientists) was VERY CAUTIOUS in what he said, using words and expressions like "PROBABLY each individual follicle..." "...would SEEM to indicate..." "...SUGGEST that..." "would SEEM to refute..." "there is EVIDENCE that..." "...not SIGNIFICANTLY related..."

Does that sound to you like Orentreich is making dogmatic statements about donor dominance?? Come on Stephen, you just can't stand it that even Orentreich himself is allowing himself a bit of wiggle-room! The very fact that you would try to make such a big deal out of newer evidence showing that maybe there ARE in fact other very mild "local" influences on hair growth (as opposed to the 90% or so represented by donor dominance) just shows how desperate you are to discredit the standard theory of hairloss, in favor of your own eccentric theory. You desperately want the standard theory to be an "all or nothing" theory, so that you can convince yourself and others that you've destroyed it, just because it's 90% accurate, but not 100%!!

Bryan

 

[Old Baldy]

That was the term they used Bryan! I couldn't remember. "Alopecia Prematura"!! Wow Doctor., premature balding. What an advanced base of knowledge you doctors have, got any snakeoil to sell me!? (i.e., circa 1960)

See you young guys, that's how it was back when Bryan and I were kids. "Premature balding", even a snot nosed, stupid a** 10 year old kid like myself could have come up with that one. (Of course Bryan was about 30 then. )

Sorry, I just needed to vent. Carry on guys.

 

[Bryan]

I wonder if a certain other little medical problem was referred to as "ejaculatoria prematura" in those days!

Bryan

 

[Old Baldy]

:shock:

 

[S Foote.]

I will concede that my term `maintaining' the effect might have been misleading, so i will answer your question as specificaly as i can. But first!

If your question is going where i think it is going, you are suggesting that once these cells are cultured in-vitro, they then `recover' from any prior contact inhibition in-vivo. So how can TGF beta 1 be `maintaining' this?

Is that your point Bryan?

Yes, that's part of my point. In that study you quoted before which showed that contact inhibition has the same growth inhibitive effect as androgens in some particular cell line, you failed to acknowledge that the effect of the contact inhibition eventually WORE OFF in a matter of a few hours after the removal of the contact inhibition itself. If androgens cause exactly the same effect as contact inhibition in those cells, then it's unclear exactly what those researchers meant when they said that androgens "maintained" the effect of contact inhibition. I strongly suspect that it was just a very poor and confusing choice of words on the part of the person who wrote that abstract.

In any event, balding hair follicles in culture show their sensitivity to androgens for DAYS in culture with a complete absence of any contact inhibition, not for just a few HOURS like those cells did in that study. And the most important point of all is that you still haven't found any evidence that the growth inhibition of balding scalp hair follicles comes from alleged "contact inhibition", rather than the clearly demonstrated stimulation of TGF beta-1 by androgens. It's not good enough just to show that another proposed mechanism _could_ have produced a similar result, you have to provide evidence that the other proposed mechanism _did_ produce that result.

Like i thought Bryan, you have missed the important point of that study!

The quoted study presumably induced contact inhibition in those cells in the petri dish. The induction of contact inhibition is often demonstrated in this way. They then did the experiments on how long it takes for cell to recover, and TGF beta 1 can effect this recovery time etc etc.

The important implication was stated by the authors, quote:
". Thus suppression of p45, cyclin D2/Cdk-4, and cyclin B1/Cdc-2 expression and/or activities is targeted both by contact inhibition and by TGF-beta 1 and may define common mechanisms through which these negative growth signals are integrated."

The important point here is `common mechanisms' Bryan!

I am not claiming that it is necessary for prior contact inhibited cells to `remain' in this condition for androgens to `maintain' this. I accept i might not have been perfectly clear before, so i will try again.

In the in-vitro hair follicle experiments, when pre-balding cells are exposed to androgens nothing happens to change them `into' balding cells. Once these follicles have `become' balding by some in-vivo process, they `THEN' react to androgens in-vitro to demonstrate reduced growth via the TGF beta-1 pathway.

So what we are sure of is that androgens are `NOT' causing this change `directly', and some other process is necessary to `allow' androgens to induce the TGF beta response in balding cells in-vitro.

The study concludes that contact inhibition and TGF beta-1 effects the same genes in the cells. So i am `SUGGESTING' that `MAYBE' prior contact inhibited follicle cells in-vivo, `COULD' have had `SOME' change induced that has altered the gene expression in these cells. Even when the cells have recovered from the original contact inhibition, they `MAY' retain some genetic alteration that `THEN' allows androgens to effect these via TGF beta-1 in-vitro.

Our original debate was about trying to explain why follicle cells in male pattern baldness show a `flipped' response to androgens in-vitro? This is my `SPECULATION' mechanism for this, but it is a valid scientific speculation because it is based on an experimentally demonstrated link with contact inhibition and TGF beta-1!!

I keep asking you to provide us with `anything at all' thats even remotely supports the notion you believe in of a `genetic clock' creating the flipped response. You can't produce anything Bryan!

Your explaination is, one day androgens don't effect male pattern baldness follicle cells, then `ABRACADABRA' one day they do!

Here's a SECOND question for you which will probably give you a little hint as to where I was going with the first one: In your estimation, what is the TGF beta-1 response to androgens in all three of the following types of hair follicles...body hair, balding scalp hair, and non-balding scalp hair?

As far as i can see from the studies Bryan, TGF beta 1 is largely produced in balding follicle DP cells in response to androgens, and acts to reduce the growth of the cells in-vitro.

If you now admit that it causes such an effect in vitro, why do you find it so hard to believe that it also happens in vivo? :wink:

Huh?? Because the in-vitro studies `prove' androgens are `NOT' creating this change! Once the cells are already transformed, `THEN' TGF beta-1 can effect them! The important thing we need to know is what is `CAUSING' the change in male pattern baldness follicle response to androgens??

If we understand this, `then' we might be able to do something about it!!

I can find no reference to TGF beta being a factor in-vitro in respect of beard or other follicles. If you have any specific info please post it.

I don't have any specific info on it, either. However, I find it odd that you didn't try to dismiss out of hand the idea that other hair follicles (beard or non-balding scalp hair) might have a _different_ TGF beta response to androgens than balding hair follicles! Is that a tacit admission on your part that maybe there really IS a fundamental difference in the way that balding follicles respond to androgens, compared to non-balding follicles?

But yet again Bryan, pre-male pattern baldness follicles do `NOT' respond any `differently' than none male pattern baldness scalp follicles, when exposed to androgens in-vitro! So there is `NO' fundamental difference in the follicles! The `difference' in androgen response is created by something else. I suggest prior contact inhibition in-vivo!

This is the whole point of this debate! Androgens do `NOT' create any changes in the pre-existing growth characteristics of `ANY' hair follicle samples in-vitro. Your `wish' that they will given enough time, just makes no sense Bryan :x

S Foote.

 

[S Foote.]

NO no no Bryan, your just making it up as you go along now!

You make your own restrictions on `wiggle room' as you put it. The theory you are supporting just doesn't `HAVE' any `wriggle room'!!!

It's even in the quote you posted above about Orentreich!! Try reading the papers you claim support your arguments! Quote:

" Probably each individual follicle is gentically predisposed to respond or not to respond to androgenic and/or other influences that inhibit its growth. "

That's it in a nutshell Bryan! According to your theory, the growth response of the follicles to androgens or anything else, is inherent within the follicle! No `wriggle room' at all there Bryan. This is the whole essence of the current `donor dominance' theory you always shout about!

ROTFLMAO, Stephen!!!

Orentreich (like other doctors and scientists) was VERY CAUTIOUS in what he said, using words and expressions like "PROBABLY each individual follicle..." "...would SEEM to indicate..." "...SUGGEST that..." "would SEEM to refute..." "there is EVIDENCE that..." "...not SIGNIFICANTLY related..."

Does that sound to you like Orentreich is making dogmatic statements about donor dominance?? Come on Stephen, you just can't stand it that even Orentreich himself is allowing himself a bit of wiggle-room! The very fact that you would try to make such a big deal out of newer evidence showing that maybe there ARE in fact other very mild "local" influences on hair growth (as opposed to the 90% or so represented by donor dominance) just shows how desperate you are to discredit the standard theory of hairloss, in favor of your own eccentric theory. You desperately want the standard theory to be an "all or nothing" theory, so that you can convince yourself and others that you've destroyed it, just because it's 90% accurate, but not 100%!!

Bryan

You are right about one thing Bryan, and that is that `good' scientists tend to keep an open mind. They don't jump to conclusions.

You on the other hand have consistantly tried to refute my questioning of the current `hypothesis', by repetedly throwing the `donor dominance' factor at me!

`YOU' are the one who has always tried to claim that my theory was wrong, simply because `donor dominance' did not allow any outside influence!!

Anyone who has read our past debates can testify to your stance on this Bryan!

But now it seems you are trying to back down from your previous `written in stone' donor dominance `gospel' 8)

Perhaps you had better start calling it "donor 90% dominance" :lol:

Ah well, at least it seems your learning something Bryan :wink:

S Foote.

 

[Bryan]

Like i thought Bryan, you have missed the important point of that study!

I have not overlooked anything at all.

The quoted study presumably induced contact inhibition in those cells in the petri dish. The induction of contact inhibition is often demonstrated in this way. They then did the experiments on how long it takes for cell to recover, and TGF beta 1 can effect this recovery time etc etc.

If TGF beta-1 produces the same effect as contact inhibition, then it's not affecting the "recovery time" from the contact inhibition. It's producing THE SAME EFFECT as the contact inhibition, but through a different mechanism.

I am not claiming that it is necessary for prior contact inhibited cells to `remain' in this condition for androgens to `maintain' this. I accept i might not have been perfectly clear before, so i will try again.

In the in-vitro hair follicle experiments, when pre-balding cells are exposed to androgens nothing happens to change them `into' balding cells. Once these follicles have `become' balding by some in-vivo process, they `THEN' react to androgens in-vitro to demonstrate reduced growth via the TGF beta-1 pathway.

So what we are sure of is that androgens are `NOT' causing this change `directly', and some other process is necessary to `allow' androgens to induce the TGF beta response in balding cells in-vitro.

The study concludes that contact inhibition and TGF beta-1 effects the same genes in the cells. So i am `SUGGESTING' that `MAYBE' prior contact inhibited follicle cells in-vivo, `COULD' have had `SOME' change induced that has altered the gene expression in these cells. Even when the cells have recovered from the original contact inhibition, they `MAY' retain some genetic alteration that `THEN' allows androgens to effect these via TGF beta-1 in-vitro.

Oh, so you think it's a PERMANENT change in the cells, and it's the contact inhibition that causes it?

Our original debate was about trying to explain why follicle cells in male pattern baldness show a `flipped' response to androgens in-vitro? This is my `SPECULATION' mechanism for this, but it is a valid scientific speculation because it is based on an experimentally demonstrated link with contact inhibition and TGF beta-1!!

I don't feel any particular need to SPECULATE about the cause of the flip-flop. Why don't we just wait until we know for sure? :wink: I'm sure scientists will eventually nail it down.

I keep asking you to provide us with `anything at all' thats even remotely supports the notion you believe in of a `genetic clock' creating the flipped response. You can't produce anything Bryan!

HUH?? You provided an example of a changed response to hormones YOURSELF, Stephen! It's the case of those cancer cells which slowly altered their response to androgens, when the supply of androgens was altered.

Your explaination is, one day androgens don't effect male pattern baldness follicle cells, then `ABRACADABRA' one day they do!

LOL!! I never said they change from one day to the next. I said they change over a period of YEARS. The devil is in the details, Stephen. I'm amazed at how fixated you are on the question of what causes the flip-flopping...

As far as i can see from the studies Bryan, TGF beta 1 is largely produced in balding follicle DP cells in response to androgens, and acts to reduce the growth of the cells in-vitro.

If you now admit that it causes such an effect in vitro, why do you find it so hard to believe that it also happens in vivo? :wink:

Huh?? Because the in-vitro studies `prove' androgens are `NOT' creating this change! Once the cells are already transformed, `THEN' TGF beta-1 can effect them! The important thing we need to know is what is `CAUSING' the change in male pattern baldness follicle response to androgens??

You didn't answer the question that I ASKED you! :evil: I didn't ask you about what CAUSES the change, I asked you about what happens AFTER the change! I asked you why you find it so difficult to believe that what clearly happens in vitro AFTER the change, also happens in vivo! Answer the question that I ASKED you, Stephen!!

Your tap-dancing around that issue seems to be a tacit admission of what is screamingly obvious to everyone else reading this forum: androgens cause a DIRECT and pernicious influence on scalp hair follicles, regardless of the exact reason(s) and etiology for it.

The important point here is not what originally CAUSES the flip-flopping in the response to androgens, although it would be fascinating to know exactly how that works. The important point is that once a man develops balding, his hair follicles ARE sensitive to androgens. I ask you again: are you now finally admitting that androgens are what are adversely affecting scalp hair follicles in balding, through TGF beta-1 and probably other pathways??

I can find no reference to TGF beta being a factor in-vitro in respect of beard or other follicles. If you have any specific info please post it.

I don't have any specific info on it, either. However, I find it odd that you didn't try to dismiss out of hand the idea that other hair follicles (beard or non-balding scalp hair) might have a _different_ TGF beta response to androgens than balding hair follicles! Is that a tacit admission on your part that maybe there really IS a fundamental difference in the way that balding follicles respond to androgens, compared to non-balding follicles?

But yet again Bryan, pre-male pattern baldness follicles do `NOT' respond any `differently' than none male pattern baldness scalp follicles, when exposed to androgens in-vitro! So there is `NO' fundamental difference in the follicles! The `difference' in androgen response is created by something else. I suggest prior contact inhibition in-vivo!

This is the whole point of this debate! Androgens do `NOT' create any changes in the pre-existing growth characteristics of `ANY' hair follicle samples in-vitro. Your `wish' that they will given enough time, just makes no sense Bryan :x

Stephen, quit harping on the original CAUSE of the change in response to androgens! We don't really know the full explanation to that, and I don't see much point in going on and on and on about it. The most important point here is not WHY hair follicles eventually become sensitive to androgens, it's simply that they DO become sensitive to them, for whatever reason(s). Let's move on from that, and acknowledge that balding scalp hair follicles miniaturize due to the direct, negative influence of androgens.

Bryan

 

[S Foote.]

Snip all the usual rubbish.

I have answered your questions about the contact inhibition/ TGF beta-1 issue now. You don't agree, fine.

As for these points:

>>Bryan wrote:
You didn't answer the question that I ASKED you! I didn't ask you about what CAUSES the change, I asked you about what happens AFTER the change! I asked you why you find it so difficult to believe that what clearly happens in vitro AFTER the change, also happens in vivo! Answer the question that I ASKED you, Stephen!! <<

No Bryan, `after the change', any effect of androgens in vitro is meaningless, without `KNOWING' what causes this change, and it aint androgens!!! Only a fool would conclude that androgens are `directly causing' this change as you do!

The `actual' time line is that androgens `DON'T' effect hair follicle cells in-vitro, until an action `NOT' related to any direct effect of androgens in-vivo, `primes' these follicles!!!!!

This is the conclusion that has to be reached according to the scientific evidence. If you don't `get' this by now Bryan, you never will!

>>Bryan wrote:
Stephen, quit harping on the original CAUSE of the change in response to androgens! We don't really know the full explanation to that, and I don't see much point in going on and on and on about it. The most important point here is not WHY hair follicles eventually become sensitive to androgens, it's simply that they DO become sensitive to them, for whatever reason(s). Let's move on from that, and acknowledge that balding scalp hair follicles miniaturize due to the direct, negative influence of androgens. <<

Your not fooling people here Bryan!
The most important question people are interested in, is "how do androgens `CREATE' male pattern baldness"????????????

The in-vitro tests clearly show that androgens do `NOT' create male pattern baldness `directly'!!

Your constant attempts to play down this all important point, is just laughable!


>>Bryan wrote:
Your tap-dancing around that issue seems to be a tacit admission of what is screamingly obvious to everyone else reading this forum: androgens cause a DIRECT and pernicious influence on scalp hair follicles, regardless of the exact reason(s) and etiology for it. <<

Androgens do `NOT' cause a DIRECT growth restricting effect on scalp follicles Bryan, the in-vitro tests `PROVE' this for God's sake!

>>Bryan wrote:
The important point here is not what originally CAUSES the flip-flopping in the response to androgens, although it would be fascinating to know exactly how that works. The important point is that once a man develops balding, his hair follicles ARE sensitive to androgens. I ask you again: are you now finally admitting that androgens are what are adversely affecting scalp hair follicles in balding, through TGF beta-1 and probably other pathways?? <<

Now i am going to ask `YOU' a question Bryan.

There is something very unique about the growth control `programing' in hair follicles compared to other `organs' I will answer your question above when `YOU' can tell me what this is???

S Foote.

 

[Bryan]

>>Bryan wrote:
The important point here is not what originally CAUSES the flip-flopping in the response to androgens, although it would be fascinating to know exactly how that works. The important point is that once a man develops balding, his hair follicles ARE sensitive to androgens. I ask you again: are you now finally admitting that androgens are what are adversely affecting scalp hair follicles in balding, through TGF beta-1 and probably other pathways?? <<

Now i am going to ask `YOU' a question Bryan.

There is something very unique about the growth control `programing' in hair follicles compared to other `organs' I will answer your question above when `YOU' can tell me what this is???

LOL!! I'm not sure what you're driving at, so I guess that's going to be your PERFECT excuse not to answer my question above, right?

Bryan

 

[S Foote.]

>>Bryan wrote:
The important point here is not what originally CAUSES the flip-flopping in the response to androgens, although it would be fascinating to know exactly how that works. The important point is that once a man develops balding, his hair follicles ARE sensitive to androgens. I ask you again: are you now finally admitting that androgens are what are adversely affecting scalp hair follicles in balding, through TGF beta-1 and probably other pathways?? <<

Now i am going to ask `YOU' a question Bryan.

There is something very unique about the growth control `programing' in hair follicles compared to other `organs' I will answer your question above when `YOU' can tell me what this is???

LOL!! I'm not sure what you're driving at, so I guess that's going to be your PERFECT excuse not to answer my question above, right?

Bryan

Bryan the `unique' growth characteristics of follicle cells, puts the role of TGF beta-1 in the right context when talking about in-vitro studies!

So please answer my question!

I have no problem answering yours, you ask quote:

"I ask you again: are you now finally admitting that androgens are what are adversely affecting scalp hair follicles in balding, through TGF beta-1 and probably other pathways?? "

No, i think the androgen mediated expression of TGF beta-1 in `balding' cells in-vitro, is dangerously misleading. I don't think this is the `cause' of androgen mediated male pattern baldness `in-vivo', or even a maintaining factor `in-vivo'.

I have this opinion for a number of reasons, relating to my question to you above! So please tell me what is unique about follicle growth compared to other tissues Bryan?

S Foote,

 

[Bryan]

I already replied to you before. I told you I don't know what you're driving at.

Bryan

 

[S Foote.]

I already replied to you before. I told you I don't know what you're driving at.

Bryan

OK Bryan, i will outline the points.

What is unique about hair follicle cells, is that their growth cycle is a one way street anyway!

In any other tissue, as cells die they are replaced locally and the tissue is repaired.

Each anagen regrowth of hair follicles however, involves the production of a `brand new batch' of follicle cells from stem cells. These `new' cells must also be pre-programed to respond to a specific `death' signal.

Why, because `all' these cells `die' at the same time in catagen. This just has to be through a particular signal that doesn't effect other cells. The dermal cells around the follicles are not effected, so the pre-programing and the `signal' must be unique to the hair follicles to explain the normal hair cycle.

So it is very likely that anything that may effect the genes linked with follicle growth, are going to have some kind of permanent effect on that particular `batch' of cells.

Thats point one.

Point two:

TGF beta-1 is implicated as one of the factors in the induction of catagen in `ALL' hair follicles. http://www.fasebj.org/cgi/content/full/14/5/752

Quote:
" (TGF-ß1) has been proposed to play an important role in catagen regulation. This is suggested, for example, by maximal expression of TGF-ß1 and its receptors during late anagen and the onset of catagen of the hair cycle."

So anything that induces restricted growth in-vivo (like contact inhibition), is likely to induce the potential for increased expression of TGF beta-1 in these cells. Again, there is a link in the genes used by contact inhibition and TGF beta-1.

Point three:

When hair follicle cells are cultured for in-vitro experiments, they reduce their ability to produce androgen receptors. They are then `seeded' with `artificial' androgen receptors. http://www.fasebj.org/cgi/content/full/16/14/1967

Quote:
"The addition of 10-9 M R1881 showed no significant influence on the proliferation of KCs in the coculture. We then assumed that in vitro cultivation of DPCs might alter the expression level of androgen receptor (AR). Semiquantitative RT-PCR showed that AR mRNA in DPCs from Androgenetic Alopecia was decreased during subcultivation from the third to ninth passage. To solve this problem, AR was overexpressed in the DPCs by transfecting the AR expression vector pSG5-AR."

Leaving apart the fact that this is a very basic `cheat', that cannot possibly reflect the cells androgen receptor production in-vivo, there is a larger problem!!

In changing the expression of androgen receptors in culture, it is clear that the culturing process `ITSELF' is changing the expression of the genes relating to AR production. So what other gene expression is being changed in culture?

How can we possibly rely on anything involving in-vitro studies knowing this!!

Just a few things for you to think about Bryan 8)

S Foote.

 

[Bryan]

I don't really have any problem with your points 1 and 2, and I have no comment on them. Continuing on with point 3:

Point three:

When hair follicle cells are cultured for in-vitro experiments, they reduce their ability to produce androgen receptors. They are then `seeded' with `artificial' androgen receptors. http://www.fasebj.org/cgi/content/full/16/14/1967

Leaving apart the fact that this is a very basic `cheat', that cannot possibly reflect the cells androgen receptor production in-vivo, there is a larger problem!!

In changing the expression of androgen receptors in culture, it is clear that the culturing process `ITSELF' is changing the expression of the genes relating to AR production. So what other gene expression is being changed in culture?

Here's another possibility that you've overlooked: human hair follicles apparently start to lose their ability to express 5a-reductase type 2 when they're cultured in vitro (that's from a recent Japanese study which I've cited a few times lately). I'm surprised you missed THAT one! :wink:

BTW, it's important to keep in mind that your cited study above was only in mouse follicles. It would be interesting to know to what extent (if any) that it's also true of HUMAN hair follicles.

How can we possibly rely on anything involving in-vitro studies knowing this!!

I agree that it's a good point to keep in mind, but I doubt that the in vitro situation varies from the in vivo situation to any really serious extent. Remember, androgen receptors weren't ELIMINATED in culture, just REDUCED.

The simple fact that hair follicles respond to androgens in vitro the same way that they respond in vivo is extremely compelling.

Bryan