Insulin resistance, PCOS, and male pattern baldness

[S Foote.]

No. I've never heard that only DP cells have androgen receptors. I'm asking you for a reference or citation to support that claim.

Choose any in-vitro follicle cell study you like Bryan. If other follicle cells apart from DP cells have androgen receptors, they would have been refered to in these studies surely?

If you can show that other follicle cells have androgen receptors, dont be shy.

As I've already said, I don't recall any studies that had any such a finding, one way or the other. One rather authoritative source which I've quoted over the years (David Whiting's "Male Pattern Hair Loss: Current Understanding") made no mention of such a claim. So once again, I'm asking YOU to tell ME where you heard that claim. Don't be shy.

OK, this is the situation as i understand it.

http://www.ncbi.nlm.nih.gov/pubmed/9496234

Quote:

" androgens are believed to act on the epithelial hair follicle via the mesenchyme-derived dermal papilla."

http://www.androgeneticalopecia.com/hai ... tors.shtml

Quote:

"The primary location for the androgen receptor in hair appears to be the dermal papillae in both anagen and telogen hairs. The androgen receptor has been found to be present in dermal sheath cells, supporting the concept that dermal sheath cells can replace dermal papilla cells even in androgen-dependent follicles"

My question is, if androgen receptors only exist in DP and dermal sheath cells, how can androgens directly effect progenitor cells as described in the posted study? http://www.jci.org/articles/view/44478#SEC3

These cells are the next step from stem cells, dont have androgen receptors, and exist "BEFORE" other cell lines that may send out growth restriction signals (according to the direct effect theory).

So how can the direct theory explain how early progenitor cells can be reduced in number by the direct androgen effect ?

Care to respond without ranting Bryan?

 

[Bryan]

Goodness gracious, is THAT your huge moment of triumph, merely pointing out that I hadn't remembered a particular passage from a 3- or 4-page discussion by several scientists? Is THAT what makes you think I'm a "sham", that I'm trying to "mislead" people, and that you've "busted" me, and after I had repeatedly asked you to answer my question about that issue??

If THAT is all it takes for you to feel good, Stephen, enjoy it while you can!! :mrgreen: :mrgreen: :mrgreen:

Your not fooling anyone with this Bryan, people can read in this thread that you ranted at me claiming thatMPB was not refered to in the Falk link, and so it was not rellevant to the brain cooling issue.

It clearly was, and the scientists explained why scalp sweating was not important in brain cooling, which was my original point.

What the hell are you talking about?? :dunno: As I've pointed out numerous times, Cabanac and Brinnell clearly describe in their 1988 paper the experiments they did showing that scalp cooling is significant in general cooling of the area of the head (presumably including the brain). Why do you keep harping on all of this? :dunno:

http://www.hairsite.com/hair-loss/forum ... 51409.html[/url]

It was in that post that he made his comment about you Bryan! Quote:

"The other important thing about your article is that you provide a method
to test its validity, That is not something that eccentric people do (I saw
that unfortunate comment about your posting which came out of the blue and I was surprised that a seemingly intelligent person would resort to such
insults for no reason and without apparent provocation). Eccentric people
are beyond proving their statements and they are also never wrong (at least
they will never admit to being wrong)"

Says it all [/quote:3r8cwtsn]

It doesn't say anything at all about what I specifically asked you about. You haven't done EITHER of the two things I requested of you (sound familiar?). I asked you what Dr. Bazan and Dr. Yechiel thought about your theory, and you haven't done that (the link you provided is about various other things...sound familiar how confused you are when it comes to providing links?). I asked you to tell me what Dr. Yechiel thinks about my "rantings", but you haven't really done that (the text you provided isn't in the link, either...maybe it's from some other link). You seem VERY confused.

[quote="S Foote.":3r8cwtsn]Point two, if you are so confident about this "slam dunk" Sawaya study, why wont you post this? Talk is cheap :whistle:

I've already posted it a long time ago, back when we were talking about this stuff a few years ago. It had to do with Sawaya's careful measurement of various follicular androgen-related cellular substances and growth-components, and how they were greatly affected by the application (or non-application) of RU58841. That's what was so convincing, the other poster called it a "slam dunk" that it's the direct action of androgens on scalp hair follicles which suppresses their growth.

Still no link then I pressume this was another of the irrelevant in-vitro studies. Irrelevant for two reasons, first follicle cells behave very differently in-vitro than in-vivo, even in the complete absence of androgens. Even the culture method itself changes characteristics.

{snip long, pointless study}

Secondly the well discussed immuno mouse study were human male pattern baldness follicles regrow (you know the one i mean ) completely overruled any rellevance of the in-vitro studies as i and others have explained to you many times.

So much for your great "slam dunk"[/quote:3r8cwtsn]

Are you going to write to Dr. Sawaya again to tell her that there's no "relevance" to any of her in vitro studies?? :mrgreen:

 

[Bryan]

http://www.androgeneticalopecia.com/hair-loss-biology/hair-loss-androgen-receptors.shtml

Quote:

"The primary location for the androgen receptor in hair appears to be the dermal papillae in both anagen and telogen hairs. The androgen receptor has been found to be present in dermal sheath cells, supporting the concept that dermal sheath cells can replace dermal papilla cells even in androgen-dependent follicles"

Note that even the study above says that the dermal papilla is only the primary location of the androgen receptor, not the only location. So am I correct in assuming that your claim in previous posts about its being the only location for the androgen receptor came straight out of your ***? :dunno:

 

[armandein]

Review
Localization of sex steroid receptors in human skin
G. Pelletier and L. Ren
Oncology and Molecular Endocrinology Research Center,
Centre de recherche du Centre Hospitalier de l’Université Laval (CRCHUL), Québec, Québec, Canada


http://www.hh.um.es/pdf/Vol_19/19_2/Pel ... 6-2004.pdf

Hope this helps!

Then, AR are located in dermal papilla and sebaceous gland

 

[S Foote.]

Review
Localization of sex steroid receptors in human skin
G. Pelletier and L. Ren
Oncology and Molecular Endocrinology Research Center,
Centre de recherche du Centre Hospitalier de l’Université Laval (CRCHUL), Québec, Québec, Canada


http://www.hh.um.es/pdf/Vol_19/19_2/Pel ... 6-2004.pdf

Hope this helps!

Thanks for the link.

 

[S Foote.]

Goodness gracious, is THAT your huge moment of triumph, merely pointing out that I hadn't remembered a particular passage from a 3- or 4-page discussion by several scientists? Is THAT what makes you think I'm a "sham", that I'm trying to "mislead" people, and that you've "busted" me, and after I had repeatedly asked you to answer my question about that issue??

If THAT is all it takes for you to feel good, Stephen, enjoy it while you can!! :mrgreen: :mrgreen: :mrgreen:

Your not fooling anyone with this Bryan, people can read in this thread that you ranted at me claiming thatMPB was not refered to in the Falk link, and so it was not rellevant to the brain cooling issue.

It clearly was, and the scientists explained why scalp sweating was not important in brain cooling, which was my original point.

What the hell are you talking about?? :dunno: As I've pointed out numerous times, Cabanac and Brinnell clearly describe in their 1988 paper the experiments they did showing that scalp cooling is significant in general cooling of the area of the head (presumably including the brain). Why do you keep harping on all of this? :dunno:

"Presumably including the brain"

No Bryan, cant you read!! That was the whole point of the Falk critique you have had so much trouble understanding. Sweating on the scalp does nothing to cool the brain, this is why male pattern baldness did not have to evolve for this reason as the theory you support tries to claim :whistle:

http://www.hairsite.com/hair-loss/forum ... 51409.html[/url]

It was in that post that he made his comment about you Bryan! Quote:

"The other important thing about your article is that you provide a method
to test its validity, That is not something that eccentric people do (I saw
that unfortunate comment about your posting which came out of the blue and I was surprised that a seemingly intelligent person would resort to such
insults for no reason and without apparent provocation). Eccentric people
are beyond proving their statements and they are also never wrong (at least
they will never admit to being wrong)"

Says it all [/quote:18rj6ngk]

It doesn't say anything at all about what I specifically asked you about. You haven't done EITHER of the two things I requested of you (sound familiar?). I asked you what Dr. Bazan and Dr. Yechiel thought about your theory, and you haven't done that (the link you provided is about various other things...sound familiar how confused you are when it comes to providing links?). I asked you to tell me what Dr. Yechiel thinks about my "rantings", but you haven't really done that (the text you provided isn't in the link, either...maybe it's from some other link). You seem VERY confused.

You have definately lost the plot now Bryan :dunno:

I dont know what you hope to achieve here Bryan, have you now become so arrogant on hair loss forums that you think you can say black is white and people will just believe you!

People can see the reality for themselves. The reason other people dont join in when we have these debates, is because they know if they dont agree with you they get the same unfounded sarcastic verbal abuse i get!

I'am sorry if i didn't include Dr Bazans comments about my theory here they are quote:

"Dear Stephen:
Your note is very interesting. I have been following your work on the hydraulics of tissue (regarding mostly on scalp physiology).
I find your work is brilliant and it must be continued since it may open one of the gates we need for solving the problem.
Our research deals with some of the proposed ideas. We find contact inhibition is a true factor in the dermal model. In respect to HM, and particularly my own method that is called SIT (scalp impregnation therapy) the life expectancy and normal cycling of the follicular complex is of utmost importance. We expect an anagen telogen catagen cycle to be repetitive and self adjusting to the environment while conserving donor dominance. We have so much to do. Keep it up.
Best of luck (and hard work),

Dr. Carl
http://www.itzan.com
(Mexico)"

I suppose this is just a fantasy as well :whistle:

[quote="S Foote.]

[quote="S Foote.":18rj6ngk]Point two, if you are so confident about this "slam dunk" Sawaya study, why wont you post this? Talk is cheap :whistle:

I've already posted it a long time ago, back when we were talking about this stuff a few years ago. It had to do with Sawaya's careful measurement of various follicular androgen-related cellular substances and growth-components, and how they were greatly affected by the application (or non-application) of RU58841. That's what was so convincing, the other poster called it a "slam dunk" that it's the direct action of androgens on scalp hair follicles which suppresses their growth.

Still no link then I pressume this was another of the irrelevant in-vitro studies. Irrelevant for two reasons, first follicle cells behave very differently in-vitro than in-vivo, even in the complete absence of androgens. Even the culture method itself changes characteristics.

{snip long, pointless study}

Secondly the well discussed immuno mouse study were human male pattern baldness follicles regrow (you know the one i mean ) completely overruled any rellevance of the in-vitro studies as i and others have explained to you many times.

So much for your great "slam dunk"[/quote:18rj6ngk]

Are you going to write to Dr. Sawaya again to tell her that there's no "relevance" to any of her in vitro studies?? :mrgreen:

Marty Sawaya is smart enough to know that you cannot properly replicate the living tissue in a test tube, and knowledge moves on.

 

[S Foote.]

http://www.androgeneticalopecia.com/hair-loss-biology/hair-loss-androgen-receptors.shtml

Quote:

"The primary location for the androgen receptor in hair appears to be the dermal papillae in both anagen and telogen hairs. The androgen receptor has been found to be present in dermal sheath cells, supporting the concept that dermal sheath cells can replace dermal papilla cells even in androgen-dependent follicles"

Note that even the study above says that the dermal papilla is only the primary location of the androgen receptor, not the only location. So am I correct in assuming that your claim in previous posts about its being the only location for the androgen receptor came straight out of your ***? :dunno:

Thats why i said as far as i know? I expected that you understood the theory you support, and would "enlighten"l me about all the cell types in follicles that have androgen receptors. I had credited you with some inteligence, obviously i was wrong, and i won't be making that mistake again!!


You just don't want to try to explain how androgens could "directly" reduce numbers of progenitor cell in male pattern baldness follicles as in the linked study.

I am pretty sure these cells dont have androgen receptors, so exlain whats going on?

(Cue yet more distractions and abuse from Bryan)

 

[balder]

Somehow, it appears that scalp hair follicles on the galea region of scalp, become "sensitive" to androgens and miniaturize, eventually becoming almost microscopic vellus hairs. Sometimes a few strands of healthy hairs exist in a region of advanced baldness then a few years later even those hairs will be gone. Don't tell me those stubborn stray hairs had a different genetic clock!

It seems that hairs are not genetically programed to fall out but instead, those hairs becomes sensitive to androgens as if they are having an allergic reaction to androgens or something associated with androgens. So if a balding follicle is transplanted to somewhere else, it will still continue to bald once the sensitivity switch has been turned on.

But, balding follicles transplanted on to the backs of immune deficient mice mysteriously regrow. So it seems that the allergic-like reaction to the association with androgens is caused by the immune system.

 

[freakout]

... So it seems that the allergic-like reaction to the association with androgens is caused by the immune system.

Hair follicles are immune-privileged.

If ever there is an immune response, it's occuring outside the follicles perhaps the surrounding tissue or anywhere in the pilosebaceous unit except the hair follicles. But an immune response is merely a RESPONSE. A response is ellicited by something and caused by something.

There are reports on some patients reqrowing hair after taking immune-suppresant drugs. Still, the question is: why men only?

Androgens and the X chromosome are NOT the only differences between men and women.

 

[hairhoper]

You just don't want to try to explain how androgens could "directly" reduce numbers of progenitor cell in male pattern baldness follicles as in the linked study.

The progenitor cell study is an attempt to explain the mechanism (or at least one link in it) by which genetically predisposed follicles are sensitive to androgens.

Nobody claimed progenitor cells are reduced by androgens.

 

[S Foote.]

Somehow, it appears that scalp hair follicles on the galea region of scalp, become "sensitive" to androgens and miniaturize, eventually becoming almost microscopic vellus hairs. Sometimes a few strands of healthy hairs exist in a region of advanced baldness then a few years later even those hairs will be gone. Don't tell me those stubborn stray hairs had a different genetic clock!

It seems that hairs are not genetically programed to fall out but instead, those hairs becomes sensitive to androgens as if they are having an allergic reaction to androgens or something associated with androgens. So if a balding follicle is transplanted to somewhere else, it will still continue to bald once the sensitivity switch has been turned on.

But, balding follicles transplanted on to the backs of immune deficient mice mysteriously regrow. So it seems that the allergic-like reaction to the association with androgens is caused by the immune system.

You raise some good points about the male pattern baldness paradox. None of this seems to have a common link. I suggest there is one however.

If as i propose, hair follicle growth is restricted in male pattern baldness by contact inhibition caused by increased pressure in the dermal tissue, this would only have its effect on new anagen follicle growth. During such an increase in pressure, existing already grown anagen follicles are not affected untill the next hair cycle. This would explain why all hair is not lost at the same time, and some follicles can show no change for years. The human scalp hair anagen period can last for years.

I think the "continue to bald" reference you make refers to Nordstroms study. This is the "follicles continue to do their thing" regardless of where they are, or the so called donor dominance Idea. This does not automaticaly mean the mechanism is locked into the follicles themselves. Nordstrom himself recognised this in this paper, when he said this could be an effect "very close to the follicle".

In my theory put simply, the follicles tend to remain in the as transplanted state because of the healing process. This produces fibrose scar tissue around the follicles, that reinforces the follicles "space". In effect the transplanted follicle is much less effected by any outside pressure, and remains in the as transplanted state (donor dominance).

What i think is happening in the immune deficient mouse study, is the healing is abnormal because of the immune status. There is no reinforced "cage" around the follicles, and follicle size can change according to the pressure around it, in this case a reduced pressure and enlargement happens.

In my opinion the normal contact inhibition of follicle growth, and its related pressure factors explain the paradox in male pattern baldness.

We also have to consider that if androgens are "locking down" follicle growth at the follicles genetic level, how can anything that does not effect androgens make any difference? Minoxidil for example.

My theory predicts that anything that reduces scalp fluid pressure in male pattern baldness, will increase hair growth.

One of the latest male pattern baldness treatment possibilities is Latanoprost and similiar drugs. What was Latanoprost developed to do? reduce tissue fluid pressure. The very well respected hairloss researcher Hideo Uno was involved in a hair growth study using Latanoprost, and it is interesting to read some background reported in this study.

http://www.google.co.uk/#hair loss=en&xhr=t&q= ... 68&bih=819

Quote:

"Latanoprost, a prostaglandin F2a analogue, is a selective
FP prostanoid receptor agonist. This drug is known to
profoundly reduce intraocular pressure and is used as
an eye drug to treat glaucoma. Although latanoprost
has no major adverse side eVects, the patients receiving
the medication have noticed an increased number,
length, thickness, and darkening of eyelashes and hair
in the medial canthal region (1–3 ). Among numerous
reports on clinical and basic pharmacological aspects of
latanoprost, the major actions related to hypertrichotic
eVects are considered to be peripheral vasorelaxation
and melanogenesis (1, 4–11). Agents that induce potent
hypertrichotic eVects are known as peripheral vasodilators
that act as potassium-channel openers, such as
minoxidil and diazoxide. Minoxidil, used originally for
hypertensive treatment, is employed topically for the
treatment of human androgenetic alopecia (malepatterned
baldness). "

I think it is important to emphasize this section quote:

" Agents that induce potent
hypertrichotic eVects are known as peripheral vasodilators
that act as potassium-channel openers, such as
minoxidil and diazoxide"

Peripheral vasodilators allow a reduction in tissue fluid pressures in surface tissue, that is around the hair follicles.

This is the common factor in these treatments for male pattern baldness.

 

[S Foote.]

You just don't want to try to explain how androgens could "directly" reduce numbers of progenitor cell in male pattern baldness follicles as in the linked study.

The progenitor cell study is an attempt to explain the mechanism (or at least one link in it) by which genetically predisposed follicles are sensitive to androgens.

Nobody claimed progenitor cells are reduced by androgens.

Yes which is related to my point about this study.

How then are progenitor cells reduced in androgen related hair loss?

 

[Jacob]

Hey S Foote..I just noticed this: http://www.phyto-stem.com/web/HairLossTheory.aspx

Some cool pics

 

[armandein]

If as i propose, hair follicle growth is restricted in male pattern baldness by contact inhibition caused by increased pressure in the dermal tissue, this would only have its effect on new anagen follicle growth. During such an increase in pressure, existing already grown anagen follicles are not affected untill the next hair cycle. This would explain why all hair is not lost at the same time, and some follicles can show no change for years. The human scalp hair anagen period can last for years.
(snipped)

In my opinion the normal contact inhibition of follicle growth, and its related pressure factors explain the paradox in male pattern baldness.

We also have to consider that if androgens are "locking down" follicle growth at the follicles genetic level, how can anything that does not effect androgens make any difference? Minoxidil for example.

My theory predicts that anything that reduces scalp fluid pressure in male pattern baldness, will increase hair growth.

Hi Foote.
Do you think if hardened sebum an contribute on the contact inhibition supossed process?

 

[hairhoper]

[quote="S Foote.":zu0iuwjt]You just don't want to try to explain how androgens could "directly" reduce numbers of progenitor cell in male pattern baldness follicles as in the linked study.

The progenitor cell study is an attempt to explain the mechanism (or at least one link in it) by which genetically predisposed follicles are sensitive to androgens.

Nobody claimed progenitor cells are reduced by androgens.

Yes which is related to my point about this study.

How then are progenitor cells reduced in androgen related hair loss?[/quote:zu0iuwjt]

Genetically, but how is not yet known.

 

[hairhoper]

It is my understanding (which should make you suspect to begin with ) that at the initiation of the anagen phase, of a follicle, from the telogen phase, not only is the stage being set for the "current" hair growth, but also, for future hair growth.

If Androgenetic Alopecia is an "event", and not a "process" (ie: once it starts in the follicle, it can only be be stopped by castration....and perhaps delayed by some degree by drugs or other methods) Then the direct effect of androgen on the current hair follicle effects the "precursors" of the hair to come.

Clarification of this thought would be appreciated! :dunno:

I can't clarify that because it is nonsense.

 

[hairhoper]

Then the direct effect of androgen on the current hair follicle effects the "precursors" of the hair to come.

What does that mean?

What are you getting at?

 

[freakout]

In regards to immunity of the hair follicle.....could someone explain Steve Jobs situation to me....

http://www.allaboutstevejobs.com/pics/l ... -1999.html

Is it plausible to say male pattern baldness is multi-causal in addition to multifactorial - the reason no one could pin it down?

Since when did Steve Jobs begin taking immune-suppresant drugs? His case is obvkously NOT immune related.

Are you going to laugh if I tell you sitting can kill you?

 

[hairhoper]

Yes.

 

[freakout]

idontwanttobebalding, Are you looking for a 'cure' or THE cause? Rather analysing the pathology, finding what's causing YOURS and preventing it from occuring would allow hair follicles to fix themselves.