What type of persons are more vulnerable to hairloss?

[michael barry]

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[docj077]

Michael,

Thanks for the post. However, that didn't give me the information that I needed. That study pretty much proves that male pattern baldness exists at the cellular level and does not require the action of different tissues outside of the hair follicle in order to occur. All that is required is the secondary mediators produced by balding dermal papillae cells. If it was the wells causing contact inhibition, then all hair would be growth inhibited.

Hair growth is not inhibited with normal dermal papillae cells. However, hair growth IS inhibited in the presence of dermal papillae cells that are from balding scalp. Obviously, something is different at the molecular level and the only difference that I can see would have to be within the receptor itself.

Thanks for posting that, but Mr. Foote needs to do his own work. I read through the methods and it makes no mention of the addition of androgen receptors at any point during that experiment, and yet, androgens still inhibited hair growth in the presence of dermal papillae cells from balding scalp as they added testosterone with or without RU 58841 directly to the cultures.

 

[michael barry]

Doctor!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!

Im sorry, I hope you didn't waste ten minutes reading the above. Its the wrong article (its been a long time since these debates between Stephen and Bryan) THIS is the article, which is heavy on TGF beta (you'll be pleased)



http://www.nature.com/jidsp/journal/v8/ ... 0093a.html

 

[Bryan]

I think I have the article that Stephen is referring to where androgen receptors had to be overexpressed on purpose for experimental integrity due to the fact that their expression was degenerating during multiple passages. I'll just cut and paste it for you both.

Actually, Michael, there's nothing in that one about altering the cell cultures to overexpress androgen receptors. I'll look around and see if I can find one of the ones in which they did that.

In the meantime, maybe it would be better to delete this one, just to save some space in the thread?

Edit: Oops! I see you already noticed yourself that it's the wrong one!

 

[docj077]

Doctor!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!

Im sorry, I hope you didn't waste ten minutes reading the above. Its the wrong article (its been a long time since these debates between Stephen and Bryan) THIS is the article, which is heavy on TGF beta (you'll be pleased)



http://www.nature.com/jidsp/journal/v8/ ... 0093a.html

Well, that article you posted above was still very interesting. It clearly demonstrated that hair loss exists at the cellular level and doesn't require inhibition through other tissues.

Here is the problem that I have with the study. This is going to sound like I'm tearing apart the article, but this is what needs to be done.

The keratinocytes still obviously produced products from the defective androgen receptor gene as the AR RNA level was decreased, but not reduced to zero. So, when they inserted the vector carrying the AR receptor gene (which, by the way, they don't tell us if it's defective or not), they simply potentiated the effects of defective AR RNA that is already being produced plus they overexpressed the receptor through vector insertion (a very stupid move) which means that everything they found would have been based not upon a hyperfunctional androgen receptor, but upon an overproduction of androgen receptors leading to increased androgen action when compared to normal.


"No significant effect of R1881 on the growth of KCs cocultured with DPCs from bald patients
First, we tried to reproduce the growth inhibition of KCs by androgen in cocultures of DPCs from Androgenetic Alopecia. Although the growth of KCs was stimulated by coculture with DPCs, addition of R1881 had no significant influence on the proliferation of KCs in the cocultures (data not shown). Expression levels of some genes may be modulated after cells are brought from vivo into cultures in vitro. Therefore, we assumed that in vitro cultivation of DPCs might alter the expression level of AR. By semiquantitative RT-PCR, the expression of AR mRNA had decreased during the subcultivation (Figure 1). Therefore, we overexpressed AR in DPCs and performed the subsequent experiments."




In order for that study to truly mean something and Mr. Foote to truly have an opinion about it, they HAVE TO completely knock out the androgen receptor gene in the DPCs and then insert the vector with the normal gene AND express it at normal levels. Only then should hair growth not be inhibited by actions of the receptor.



How can anyone in this thread expect to derive any information from a study that allows the defective androgen receptor to be produced and overexpresses the AR number? Both are going to lead to increased androgen action in the dermal papillae and increase TGF-beta appropriately to levels that very likely match levels in the balding human scalp.



Their little experiment works, because they are inhibiting AR RNA production or degrading it somehow, but they still end up replacing it and overexpressing it. This doesn't interfere with normal androgen receptor function or translocation into the nucleus. By using the vector, they are essentially infecting these cells with the correct gene, but avoiding the mess of trying to get it across the cell membrane and encouraging it to use its normal method of intracellular transportation by producing it the cytoplasm through the vector. I have to give them credit as they did at least one thing right.


By the way, I do like that they are finally focusing on TGF-beta more. I keep yelling that TGF-beta is the inhibitory molecule, but nobody around here wants to believe me.

 

[Bryan]

Michael,

Thanks for the post. However, that didn't give me the information that I needed. That study pretty much proves that male pattern baldness exists at the cellular level and does not require the action of different tissues outside of the hair follicle in order to occur. All that is required is the secondary mediators produced by balding dermal papillae cells. If it was the wells causing contact inhibition, then all hair would be growth inhibited.

So familiar I am with the way Mr. Foote's mind works, I can already tell you what his response to that study is: he thinks that the fundamental cause of the slow deterioration in hair growth in male pattern baldness is contact inhibition, and that the in vitro results in the study above (and other similar studies) are due to the contact inhibition CAUSING a change in the way that those cells respond to androgens. In other words, the change in response to androgens is just sort of a side-effect of contact inhibition! Seriously, that's what he really believes, and that's how he tries to explain the Uno study above! :wink:

Hair growth is not inhibited with normal dermal papillae cells. However, hair growth IS inhibited in the presence of dermal papillae cells that are from balding scalp. Obviously, something is different at the molecular level and the only difference that I can see would have to be within the receptor itself.

Docj, I think it's a little misleading and confusing to focus too much on the polymorhpisms of the androgen receptor which are associated with balding. Those only affect the intensity of the androgenic stimulus, which doesn't address the more fundamental question of why it is that body hair dermal papillae and scalp hair dermal papillae have opposite RESPONSES to androgens.

 

[docj077]

Michael,

Thanks for the post. However, that didn't give me the information that I needed. That study pretty much proves that male pattern baldness exists at the cellular level and does not require the action of different tissues outside of the hair follicle in order to occur. All that is required is the secondary mediators produced by balding dermal papillae cells. If it was the wells causing contact inhibition, then all hair would be growth inhibited.

So familiar I am with the way Mr. Foote's mind works, I can already tell you what his response to that study is: he thinks that the fundamental cause of the slow deterioration in hair growth in male pattern baldness is contact inhibition, and that the in vitro results in the study above (and other similar studies) are due to the contact inhibition CAUSING a change in the way that those cells respond to androgens. In other words, the change in response to androgens is just sort of a side-effect of contact inhibition! Seriously, that's what he really believes, and that's how he tries to explain the Uno study above! :wink:

Hair growth is not inhibited with normal dermal papillae cells. However, hair growth IS inhibited in the presence of dermal papillae cells that are from balding scalp. Obviously, something is different at the molecular level and the only difference that I can see would have to be within the receptor itself.

Docj, I think it's a little misleading and confusing to focus too much on the polymorhpisms of the androgen receptor which are associated with balding. Those only affect the intensity of the androgenic stimulus, which doesn't address the more fundamental question of why it is that body hair dermal papillae and scalp hair dermal papillae have such different RESPONSES to androgens.

I absolutely agree that the polymorphisms don't explain the difference. Unfortunately, we can work out what likely causes the process to occur in the scalp. I can't really tell you why it doesn't occur in the rest of the body. There is either more androgen action in the scalp and it offsets the intrinsic activity of the scalp follicles more than body hair follicles or their is an inhibitor produced in the rest of the body that we're missing. The other possibility is that the intrinsic activity of body hair is far lower (I think it is at it seems to grow slower than scalp hair) and the overstimulation of the androgen receptor in the hair follicles of the body simply brings androgen stimulation and action up to a level that still allows growth (maybe even accelerates it), but also prevents its inhibition.

Personally, I like to think that it's related to 5AR density and androgen receptor density, but I know that you don't go for such opinions. To be honest, I really don't know if 5AR and androgen receptor levels are increased in the scalp.

 

[Bryan]

How can anyone in this thread expect to derive any information from a study that allows the defective androgen receptor to be produced and overexpresses the AR number? Both are going to lead to increased androgen action in the dermal papillae and increase TGF-beta appropriately to levels that very likely match levels in the balding human scalp.

But that's exactly THE POINT of the study: to prove that balding is caused by the action of androgens on the dermal papillae of scalp hair follicles, which then causes the expression of negative growth factors which harm the whole of the follicle.

 

[michael barry]

Doctor,

Temporal hair has more androgen receptors. Ive read that and remember noting it.


Also, are you aware that scalp hair grows in "units"? There are some 4 and 5 hair "units" of hair on men's scalp. Dr. John Cole even had a close up of a pictures of a 6 hair unit (previously not thought to exist). Most follicular units are 2 and 3 hairs apiece though. I'll look around and see if I can link you a pic.

The hair in the wreath has many more "large units" of multiple hairs. The hair on top and in the vertex has many more 1 and 2 hair units. Your body hair has primarily one hair units, very occasional 2 hair units, and once in a blue moon 3 hair units.

Body hair grows kinkier and curlier. Underarm hair, eyebrow hair, and pubic hair need little/no androgen stimulis at all. Nose hair needs no androgen stimulis. I simply think body hair and head hair are different, and not just at the receptor level because body hair will not grow without androgens if they never recieve them, but head hair will grow without androgens regardless of whether they ever "get" androgens or not.


Here are some 2-3 hair follicular units under magnification,
http://www.hairlosspatientguide.com/ima ... 0units.jpg

Here is another larger pic of follicular units in the wreath area of the scalp http://www.hattingenhair.com/img/follicular_units.jpg If this were a pic of the top of the scalp, the units would simply be one's and two's (units of hair) and exclusively one's up front near the hairline. Thats the way it grows: different than body hair.

I posted some info recently indicating there is more DHT in balding scalp areas, its on one of these sites somewhere, but dont remember where.

 

[Bryan]

I absolutely agree that the polymorphisms don't explain the difference. Unfortunately, we can work out what likely causes the process to occur in the scalp. I can't really tell you why it doesn't occur in the rest of the body.

Well, frankly, the question is why isn't the effect of androgens CONSISTENT across the entire body. Why don't androgens either STIMULATE all hair follicles, or SUPPRESS all hair follicles?

There is either more androgen action in the scalp and it offsets the intrinsic activity of the scalp follicles more than body hair follicles or their is an inhibitor produced in the rest of the body that we're missing. The other possibility is that the intrinsic activity of body hair is far lower (I think it is at it seems to grow slower than scalp hair) and the overstimulation of the androgen receptor in the hair follicles of the body simply brings androgen stimulation and action up to a level that still allows growth (maybe even accelerates it), but also prevents its inhibition.

Well, I just don't see how hypothesizing a "biphasic" effect of androgens is going to work, either (a certain level of androgens being stimulating, and a different level being suppressive). I don't know of any evidence for that. I think we're still stuck with the fundamental conundrum that androgens have an intrinsically opposite effect on scalp hair follicles versus body hair follicles.

 

[docj077]

How can anyone in this thread expect to derive any information from a study that allows the defective androgen receptor to be produced and overexpresses the AR number? Both are going to lead to increased androgen action in the dermal papillae and increase TGF-beta appropriately to levels that very likely match levels in the balding human scalp.

But that's exactly THE POINT of the study: to prove that balding is caused by the action of androgens on the dermal papillae of scalp hair follicles, which then causes the expression of negative growth factors which harm the whole of the follicle.

Sorry, I'm a little under the weather right now, so my thoughts probably aren't very complete (they rarely are anyway :hairy: ). I understand that the point of the study was to prove what you've said above. I just would have done things differently. From what I've read in this thread alone, it seems that the entire process is not only androgen dependent, but also androgen receptor concentration dependent. With a low level of defective androgen receptor due to mRNA degradation or inhibition, you will get no hair growth inhibition. Only after you insert a vector containing the receptor and you overexpress it do you get a response that warrants follicular inhibition. The whole thing is androgen dependent, because it is androgen receptor dependent.

It's almost too perfect and the studies explain the process so clearly and they actually give us the conditions that are required. You either need full production of the defective androgen receptor RNA or you need to increase normal androgen receptor RNA enough with a vector to adequately prolong and increase the androgen dependent biochemical reactions. Not only is this true, but you do not need any tissue besides the follicle with dermal papillae cells from balding scalp. So, these DPCs are not contact inhibited and neither are the keratinocytes as they are removed from any inhibition, but the keratinocytes are still growth inhibited. The wells in that study that used to be above demonstrate that the wells have no real application other than to provide structural support. I forget exactly what was in the wells other than collagen. Collagen can inhibit growth, but what it will come down to is the strict action of androgens and the promotion of collagen deposition through the action of collagenase inhibition. It will not be edema that will cause the contact inhibition. It is the collagen. However, the inhibition will be the result of follicular pathophysiology and not extracellular matrix pathology.

I do not remember the study, but I believe that all the wells had collagen. If that is true, then collagen is not as potent of a growth inhibitor as many people think as it did not inhibit the growth of DPCs from non-balding scalp. That in itself would lead one to believe that it is the extrinsic and intrinsic growth signals influencing the follicle that begin the process and actually prevent hair cycling. It is the contact inhibition provided by collagen that prolongs the disease. Collagen deposition and the resulting inhibition would not take place until well into the balding process. This is quite clear as many balding men show little to no evidence of increased collagen until they have been balding for years.


As for the difference between scalp hair and body hair, I really do think that the difference is in the intrinsic activity of the follicle. With total androgen insensitivity you will still get the development of minimal pubic and axillary hair. However, the hair in the scalp will still grow longer and faster than body hair and will have no androgen response. So, there is activity in what is considered "androgen dependent" hair even without androgens. The only explanation is a difference in follicular cycling at the cellular level. Even with a defective receptor, the length and speed of cycling should be different. In the scalp, there is a must faster intrinsic response and androgens simply have more to build on. The same should not hold true in the body.

 

[Bryan]

How can anyone in this thread expect to derive any information from a study that allows the defective androgen receptor to be produced and overexpresses the AR number? Both are going to lead to increased androgen action in the dermal papillae and increase TGF-beta appropriately to levels that very likely match levels in the balding human scalp.

But that's exactly THE POINT of the study: to prove that balding is caused by the action of androgens on the dermal papillae of scalp hair follicles, which then causes the expression of negative growth factors which harm the whole of the follicle.

I understand that the point of the study was to prove what you've said above. I just would have done things differently. From what I've read in this thread alone, it seems that the entire process is not only androgen dependent, but also androgen receptor concentration dependent. With a low level of defective androgen receptor due to mRNA degradation or inhibition, you will get no hair growth inhibition. Only after you insert a vector containing the receptor and you overexpress it do you get a response that warrants follicular inhibition. The whole thing is androgen dependent, because it is androgen receptor dependent.

I feel that all of those issues have more to do with the successful treatment of balding, as opposed to what we're discussing here in this thread, which is the basic and fundamental cause of balding. Remember, this very thread was started by Armando, one of the eccentrics (along with Stephen Foote and Ernie Primeau) who deny the standard, accepted theory of male pattern baldness in favor of their own screwball theories. I feel that our mission in this specific thread is not to dwell at length on the relatively more mundane issues like just exactly how much androgen is too much for healthy hair, or which androgen receptor mutation is the worst one to have for balding, or what level of scalp 5a-reductase is excessive; our mission here should be to investigate these more basic controversies and help convince everyone (especially newbies and anybody else who may be sitting on the fence about them) of the accuracy and validity of the accepted theory of male pattern baldness, lest they fall for those other unscientific theories about contact inhibition, sebum backup, etc.

It's almost too perfect and the studies explain the process so clearly and they actually give us the conditions that are required. You either need full production of the defective androgen receptor RNA or you need to increase normal androgen receptor RNA enough with a vector to adequately prolong and increase the androgen dependent biochemical reactions. Not only is this true, but you do not need any tissue besides the follicle with dermal papillae cells from balding scalp. So, these DPCs are not contact inhibited and neither are the keratinocytes as they are removed from any inhibition, but the keratinocytes are still growth inhibited.

AMEN to that, brother!

What would you say to Stephen Foote's contention that the negative response of scalp DPCs to androgens is a secondary and irrelevant phenomenon, one that occurs only AFTER they have have been subjected to contact inhibition, and that it's really the contact inhibition itself which does the dirty work?

As for the difference between scalp hair and body hair, I really do think that the difference is in the intrinsic activity of the follicle. With total androgen insensitivity you will still get the development of minimal pubic and axillary hair. However, the hair in the scalp will still grow longer and faster than body hair and will have no androgen response. So, there is activity in what is considered "androgen dependent" hair even without androgens. The only explanation is a difference in follicular cycling at the cellular level. Even with a defective receptor, the length and speed of cycling should be different. In the scalp, there is a must faster intrinsic response and androgens simply have more to build on. The same should not hold true in the body.

I'm not entirely clear what you mean when you use terms like "intrinsic activity" and "intrinsic response". Are you saying that you feel that the opposite response to androgens of scalp hair follicles and body hair follicles is indeed intrinsic to each individual hair follicle and the specific biochemical reasons for that are unknown, or are you saying you think it's reasonable that such a difference exists, and you have a tentative hypothesis to explain it?

 

[docj077]

As for the difference between scalp hair and body hair, I really do think that the difference is in the intrinsic activity of the follicle. With total androgen insensitivity you will still get the development of minimal pubic and axillary hair. However, the hair in the scalp will still grow longer and faster than body hair and will have no androgen response. So, there is activity in what is considered "androgen dependent" hair even without androgens. The only explanation is a difference in follicular cycling at the cellular level. Even with a defective receptor, the length and speed of cycling should be different. In the scalp, there is a must faster intrinsic response and androgens simply have more to build on. The same should not hold true in the body.

I'm not entirely clear what you mean when you use terms like "intrinsic activity" and "intrinsic response". Are you saying that you feel that the opposite response to androgens of scalp hair follicles and body hair follicles is indeed intrinsic to each individual hair follicle and the specific biochemical reasons for that are unknown, or are you saying you think it's reasonable that such a difference exists, and you have a tentative hypothesis to explain it?

Not only reasonable, but I really do believe that there is an intrinsic difference. Using men with androgen insensitivity syndrome and women with hirsutism as models. As I mentioned before, men with AIS will still develop minimal pubic and axillary hair even with complete AIS. This means that there is no androgen response, and thus, no androgen mediated growth. Without androgens as a growth promoter, these men will have hair growth that is based strictly on the intrinsic nature of the follicle in a given area of the body. Obviously, the pubic hair growth is minimal, but the hair of the scalp continues to grow at rate that is far above the body hair. With that model, one can see that there is an intrinsic difference in follicle cycling and growth rate when androgen action is removed.

I also use hirsutism as a model, because it demonstrates that an increase in androgens in a woman can alter follicular cycling and change vellus hairs to terminal hairs. Without the abundance of androgen action, female body hair patterning is different from men, but with an androgen increase, hair begins to turn terminal in places like the face. So, what you do in hirsutism is take the intrinsic growth rate of a hair follicle with a vellus hair and you simply add the action of androgens. The intrinsic rate is overcome and the growth rate and type of hair becomes androgen dependent.

Even with that increase in androgens, the growth rate of the facial hair will still be less than that of scalp hair follicles. So, the only logical explanation that I can see is the intrinsic rate was different to begin with.


That's not really a hypothesis (I don't know why we try to come up with theories on a message board), but I think that it's a good example.

 

[Bryan]

Bryan.

Of course there are lot's of other factors that can and do effect hair growth. But the donor dominance claim in transplantation does not make any such allowences!

How do YOU know what donor dominance "claims" are being made in transplantation? Seriously, how do you know? Medical knowledge and opinion are dynamic things, they shift and change as we do more experiments and learn more and more. The Korean experiment has added a bit to our knowledge of hair transplantation.

If as you now claim, other factors can change the growth of so called androgen responsive follicles, yet remain androgen dependant for "most" of it's growth characteristics, the next question is obvious?

How do you "KNOW" if it's another factor causing the growth change, or a change in the androgen control? How can you measure which factor is causing the change? You just can't!

It seems extremely unlikely that some supposed "change in androgen control" would account for the increased growth in the Koren experiment, because we know that body hair isn't all THAT sensitive even to strong hormone manipulation like what you get with finasteride and dutasteride.

You are now saying that so called androgen dependant body hair can have it's androgen growth "control" overuled by external factors.

The word "overruled" is excessive. Better to say that it's supplemented by those other factors.

In your original claim about donor dominance, you quoted the case of male pattern baldness follicles transplanted to other areas retaining their growth rate as proof of your donor dominance argument.

Suppose i had said then that those male pattern baldness follicles "would" have increased their growth "IF" they had recieved other outside influences, that overuled the androgen effect you claimed? You would have jumped on me instantly!

A very important point that you keep ignoring is that the balding follicles transplanted to the arm in the Nordstrom study continued to bald at what appeared to be THE VERY SAME RATE as they did when they were still on the scalp. What would William of Ockam have said was the most likely explanation for that? :wink:

It is the current theory you support Bryan that is the problem you have here. My theory accepts external influences, yours just doesn't!

I bow to scientific evidence, which seems to clearly demonstrate that the androgenic response of individual hair follicles is maintained when they are transplanted to other areas of the body, AND there are certain local factors in some specific areas of skin that seem to have their own modest effect on growth, on top of the androgenic influence.

 

[Bryan]

Not only reasonable, but I really do believe that there is an intrinsic difference. Using men with androgen insensitivity syndrome and women with hirsutism as models. As I mentioned before, men with AIS will still develop minimal pubic and axillary hair even with complete AIS. This means that there is no androgen response, and thus, no androgen mediated growth. Without androgens as a growth promoter, these men will have hair growth that is based strictly on the intrinsic nature of the follicle in a given area of the body. Obviously, the pubic hair growth is minimal, but the hair of the scalp continues to grow at rate that is far above the body hair. With that model, one can see that there is an intrinsic difference in follicle cycling and growth rate when androgen action is removed.

Sure, but let's get back to the fundamental question: what accounts for the opposite reaction of scalp and body hair follicles to androgens? Do you have an explanation, theory, or even a hypothesis for that? That's what I was getting at before.

 

[michael barry]

Doctor,

Did you know that beard hair is the fastest growing and largest hair in the body, anywhere?


As you know, Ive looked to transexuals of both kinds to determine what role androgens play in hair growth because we have a great IN VIVO example of what happens when testosterone is either added, or taken away from skin.


Look at this picture of a WOMAN, who has used testosterone. Its disgusting, and this "thing" is some kind of p**rn star. She still has breasts and a vagina, and is covered in hair. Her beard hair is the thickest on her body, but her head hair quickly was lost (skull cap),
http://www.tlavideo.com/details/product ... =4&sn=1744

You can enlarge the image by clicking "ENLARGE THE IMAGE" below the picture. Its icky as all get out, but you get my point about beard hair. She was a woman (still is), with a thicker fuckking beard than what I have.




I hearken back to the picture of a woman whose hair thinned, but didn't bald on Oprah, when she took testosterone:
http://www2.oprah.com/tows/slide/200509 ... _102.jhtml
Twin females.

Up close: http://www2.oprah.com/tows/slide/200509 ... _103.jhtml


See the big, thick beard hairs? Larger than head hair. Note the thinning and ageing of the head hair up top? The greying?
Whats sad their is video of this "gal" when she was still a girl,
http://www2.oprah.com/tows/pastshows/20 ... 0916.jhtml
and as you can see, she was once very cute.


I have read on transexual discussion boards of "trannies" complaining that when they dont take their flutamide, their body hair COMES BACK even after having laser hair removal done once or twice years later, which is of course, very frustrating to a man who has decided to be "feminine".

Finasteride all these years didn't make me "lose" body hair, but I quit getting hairier. I'd have been a much hairier man by now if I'd not used it. Its apparent body hair only needs small androgenic stimuli to keep growing, but more than a woman (10 percent of the testosterone a man has) obviously usually has.

 

[S Foote.]

Whats up "Doctor"?

Why have you not cleared up the issue as to if you are a genuine Doctor or not? Here's a puzzle for you while you are thinking about it.

You claim some kind of faulty androgen receptor status as being the cause of male pattern baldness?

I don't claim this. There are many known AR gene polymorphisms including: the (CAG)n trinucleotide repeat, the (GGC)n trinucleotide repeat, and the R726L single nucleotide polymorphism. The defect in the androgen receptor appears to be a single nucleotide polymorphism. There are also co-receptor mutations that are well known and associated with male pattern baldness.

I see that you still lack appropriate forum manners. You know that I'm not a doctor. I'm a medical student. Big difference, but that doesn't discredit my opinion as I have many years of research experience combined with clinical experience. I always forget what your credentials are, but I'm sure that you'll remind us all of your incredible education and unparalleled research skills.

Of course you are entitled to your opinion, but you are "NOT" entitled to mislead people about the validity of your opinions by pretending to be a Doctor when your not!

Please change your handle, or i will formally protest to the admin of this site about your misrepresentation.

The in-vitro tests are often quoted as proof of the androgen action in male pattern baldness, as being "right there" within the follicles themselves. But because of the culturing process itself. the follicles cells used in these tests loose the ability to produce androgen receptors.

If this is true, then the hair follicles would lose more than just the ability to produce androgen receptors. Either transcription or translation would have to be inhibited cell-wide and if it simply a product that degrades protein, then all cellular processes would be inhibited. To expect any sort of results from such studies that use the culturing method you seem to be mentioning would be foolish at best.

Well at least we agree on something!

I am on the record as stating the pitfalls of the in-vitro test results for a number of reasons,including the one you give above.

The alternative is that the transportation machinery of the cell is somehow disrupted. But, once again, that would skew any results that are obtained using such a culturing method as one would expect inappropriate intracellular protein targeting.

I had links to specific studies that stated this, but i lost these recently (computer problems). Perhaps Michael can help with these links.

I would enjoy reading them. I don't believe you, but I'd enjoy reading them.

http://www.med.unc.edu/pharm/rjlabpg/pdfs/cocb99.pdf[/url]

Heres one thing we do have evidence for, it has been shown that contact inhibition and TGF beta-1 target the same genes in cell cycle arrest!

http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract

If the androgen effect is limited to within the follicle itself, what then causes the proven microvascular insufficiency in the male pattern baldness area?

http://www.plasreconsurg.com/pt/re/prs/ ... 44!8091!-1

Such hypoxia in "itself" is known to upregulate TGF beta-1.

http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract

Work that one out for yourself!

We also have the studies regarding lipedematous alopecia and lipedematous scalp.

Note the link with ectactic lymphatic vessels associated with cases involving hair loss!

http://alopecia.researchtoday.net/archive/1/2/66.htm

We know that hair growth varies greatly in areas of the body in the complete absense of any androgen influence. The most logical explaination for this is not any internal factor within the follicles, but an external difference in the resistence offered to anagen follicle enlargement by the surrounding tissue, through normal contact inhibition of growth.

Variable resistence from surrounding tissue would easily explain the entire range of growth in different areas from vellous to terminal, and have some purpose in mammalian evolution.

In my opinion, the overwhelming body of evidence points towards androgens effecting the dermal resistence to follicle enlargement, so changing hair growth in different areas.

If you are going to argue it is all down to differences in androgen receptors, then answer Bryans question?

What are the various differences in androgen receptors that account for the range of androgen responses in hair follicles?

Also, if people are going to claim the in-vitro studies "do" reflect what happens in-vivo, how is it that follicles in these studies that are known to be "future" male pattern baldness follicles, are not "directly" growth restricted by androgens in-vitro?

Bryan has tried to claim that these follicles need to be exposed to androgens for a while before they "then" become sensitive to androgens?

The big problem with this is the normal hair cycle, that even male pattern baldness follicles go through.

Every time a follicle cycles, it is re-built during anagen from stem cells. Stem cells have no pre- dispositions, hence the term stem cells. So where are all these "different" built in responses to androgens coming from?

Bryan claims that a period of direct exposure to androgens is needed before male pattern baldness kicks in.

If this was true, there would be no such thing as male pattern baldness, because each new anagen follicle in the male pattern baldness area would grow normally for at least long enough to be replaced by other new anagen follicles after male pattern baldness has "kicked in" in existing follicles, by a period of exposure to androgens.! (According to Bryan).

What the current theory has to prove, is that there is "some" difference in the genetic expression within hair follicles, that would allow the different responses we see to androgens, "BEFORE" androgens come into the equasion!

S Foote.

 

[S Foote.]

Bryan.

Of course there are lot's of other factors that can and do effect hair growth. But the donor dominance claim in transplantation does not make any such allowences!

How do YOU know what donor dominance "claims" are being made in transplantation? Seriously, how do you know? Medical knowledge and opinion are dynamic things, they shift and change as we do more experiments and learn more and more. The Korean experiment has added a bit to our knowledge of hair transplantation.

That was exactly my argument in the original thread Bryan! But you were the one that first made these claims about donor doninance then, that you now try to deny!!

If as you now claim, other factors can change the growth of so called androgen responsive follicles, yet remain androgen dependant for "most" of it's growth characteristics, the next question is obvious?

How do you "KNOW" if it's another factor causing the growth change, or a change in the androgen control? How can you measure which factor is causing the change? You just can't!

It seems extremely unlikely that some supposed "change in androgen control" would account for the increased growth in the Koren experiment, because we know that body hair isn't all THAT sensitive even to strong hormone manipulation like what you get with finasteride and dutasteride.

[quote="S Foote.":6a348]You are now saying that so called androgen dependant body hair can have it's androgen growth "control" overuled by external factors.

The word "overruled" is excessive. Better to say that it's supplemented by those other factors.

In your original claim about donor dominance, you quoted the case of male pattern baldness follicles transplanted to other areas retaining their growth rate as proof of your donor dominance argument.

Suppose i had said then that those male pattern baldness follicles "would" have increased their growth "IF" they had recieved other outside influences, that overuled the androgen effect you claimed? You would have jumped on me instantly!

A very important point that you keep ignoring is that the balding follicles transplanted to the arm in the Nordstrom study continued to bald at what appeared to be THE VERY SAME RATE as they did when they were still on the scalp. What would William of Ockam have said was the most likely explanation for that? :wink:

It is the current theory you support Bryan that is the problem you have here. My theory accepts external influences, yours just doesn't!

I bow to scientific evidence, which seems to clearly demonstrate that the androgenic response of individual hair follicles is maintained when they are transplanted to other areas of the body, AND there are certain local factors in some specific areas of skin that seem to have their own modest effect on growth, on top of the androgenic influence.[/quote:6a348]

The scientific evidence is very clear Bryan, but still you refuse to bow to it!

The authors of that study said the transplantation effects could be because of an effect very close to the follicle. That is in the tissue that is transplanted with the follicles. I argued this point at the time, as anyone can see in the link i provided.

But you would have none of it then, yet now you do another U turn and concede "some" external effects!

If you are just going to ignore the scientific rules of evidence when they don't suit your argument of the moment, people are not going to take you seriously!

I raised a few points in my last post to "Doctor" about the in-vitro tests and another of your "previous" claims. Am i going to see another U turn from you on that issue?

S Foote.

 

[michael barry]

Stephen,

Do you realize, that for your theory to be true, DHT must alter the lymph pumping all over the body? I have large hairs on my fingers and toes Stephen. Im a hairy man, even with a decade's usage of finasteride.


Did you look at that p**rn star "thing" Van Diesel, whose pictures I posted. "She" has hair all over herself now, even on her breasts, and a thicker beard than even I have. She is a female who has taken testosterone injects or used testosterone creams. Thats it..........Her Lymphatic profile would have had to be altered off the charts to generate that much hair, even on the extreme regions of her body. Are there any lymph pumps even present on fingers? I have hair on some fingers past the first joint on the fingers, down between the 2nd and 3rd joints past where one wears rings, etc.


Im still using that cold pack of blue ice for half an hour every day while I read the net right above my knee. After taking it off, the area remains cold for about twenty minutes. Thats almost an hour a day of pushing fluid away from the site. I'll be able to tell you in about 4 more months if pushing fluid away makes the hair grow better there.

 

[docj077]

Of course you are entitled to your opinion, but you are "NOT" entitled to mislead people about the validity of your opinions by pretending to be a Doctor when your not!

Please change your handle, or i will formally protest to the admin of this site about your misrepresentation.


S Foote.

I see that you still enjoy using personal attacks when you are backed into a corner. How immature and foolish. How many studies do you have to see and how long does modern medicine have use molecular biochemistry and the growth/inhibitory factors within the follicle itself for you to be satisfied. TGF-beta is produced within the follicle itself and no outside factors are required. Can you prove that the follicle itself is hypoxic and not just the surrounding tissue? Personally, I think that if there is hypoxia, it is due to collagen deposition and it is a process that is accompanied by prolonged male pattern baldness conditions within the scalp. By the way lipidematous alopecia is not an underlying cause of male pattern baldness.

Seriously, it makes me sad to see you stuck where you are right now. You're not beaten, but you're not right, either.

There is no such thing as microvascular insufficiency in every man with male pattern baldness and TGF-beta is not increased as a result of hypoxia in the follicle. Not every man with male pattern baldness demonstrates pathologic spongiosis (which would prove your microvascular insuffiency). Also, TGF-beta is increased due to the actions of androgens on dermal papillae cells and dermal fibroblasts. It is the only factor that truly inhibits keratinocyte function as anti-TGF-beta antibodies will completely reverse any TGF-beta produced process (which will be completely based upon the androgen response when you have only the dermal papillae and it has proper nutrition). The production of TGF-beta is androgen dependent and androgen receptor dependent. That is something that has been proven. So, I fail to understand why you think that tissue hypoxia would make a difference. There is already enough TGF-beta produced by androgen dependent mechanisms that there really is no point on focusing on any other process. Plus, as I said above, you simply have to remove the action of TGF-beta within the follicle and normal keratinocyte functioning can resume.



About your desire to report me to the admins...

That is up to you. Everybody that wants to know my credentials has asked me, so I don't see a problem. I'm a medical student with a strong research and clinical background. That's it. Between you and me, I do believe that you don't have the educational background to form an educated opinion or truly analyze medical studies.

Besides, the "Doctor" in my name was given to me by my grandfather before he died. I don't think that even you can be so heartless. A very low blow, but very typical for you.



Keep focusing on that which you "think" matters and we'll simply move ahead with what really matters.