Insulin resistance, PCOS, and male pattern baldness

[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?

Androgens may have a direct effect on progenitor cell formation.

Ah! Sorry for my tone. Had had a beer and freakout's usual drivel was annoying me.

 

[balder]

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.

Does intercellular pressure put restrictions on cell growth? Does reduction in that pressure help people become slightly taller?

http://www.lifeslittlemysteries.com/wou ... ngs--1413/

On Earth we experience the steady hand of gravity at 1 g force constantly throughout our lifetimes. On other planets in our solar system, that’s just not possible. Researchers are working on ways to make artificial gravity possible in order to make long flights easier on human bodies. According to NASA, most astronauts grow about 2 inches while they’re in space because the reduced gravity causes the fluid between vertebrae to expand. They lose the height within 10 days of returning to Earth’s crushing gravity. Because of the growth, NASA uses space suits that have extra room to accommodate the additional height.

External water pressure does not seem to restrict growth of deep sea fish though...

http://en.wikipedia.org/wiki/Deep_sea_fish

Insulin Plays Central Role In Aging. The smoking gun insulin connection to male pattern baldness is yet to be discovered though :dunno:

http://www.sciencedaily.com/releases/20 ... 064935.htm

Block the hormone's action inside a few specific cells, the study shows, and the entire body stays healthier longer. Scientists previously thought insulin triggered other hormones to achieve this effect, but Tatar and his team found that insulin regulates its own production and that it directly regulates tissue aging. The principle: Keep insulin levels low and cells are stronger, staving off infection and age-related diseases such as cancer, dementia and stroke.

 

[S Foote.]

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

Some cool pics

Thanks for that Jacob, this relationship is central to my theory of male pattern baldness as you know, and its nice to see others have noticed this. I will read the link in detail
when i have more time.

 

[S Foote.]

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?

If you are suggesting that androgens increase sebum then this restricts scalp follicle growth in some way, you also have to explain the flip side?

how does androgen related sebum production increase follicle size in other areas?

Any valid theory of androgen related hair growth has to do both.

 

[S Foote.]

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:

If what you say is true, then the male pattern baldness follicles in the immuno-mouse study would not have regrown.

According to the direct effect theory, everything was present in those transplanted male pattern baldness follicles to maintain them in that condition. And more than enough androgens in the mice (again according to the direct sensitivity claim).

 

[S Foote.]

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.

Does intercellular pressure put restrictions on cell growth?

I am talking about extracellular pressure remember.

The thing about hair follicles is that they are "hollow" pockets in the dermal tissue. This makes them sensitive to fluid pressure in dermal tissue because they are hollow.

It is not the direct fluid pressure but the fact that this would push dermal cells in towards any hollow in the tissue. There is a very simple analogy here.

Blow up a party baloon with different pressures of air. For the air think fluid pressure, for the skin of the baloon think dermal tissue. Now push a finger into the baloon to form a pocket in it.

The more pressure, the more resistence there is to the formation of a pocket.

Higher fluid pressure around the growing anagen follicle, normal contact inhibition of growth kicks in earlier, and you get a smaller follicle.

 

[hairhoper]

lulz.

 

[DarkDays]

After seeing "brain cooling" mentioned one too many times I just have to say this:

Anybody who thinks brain cooling has any reason behind it is a sexist misogynistic pig, I am sorry to say. If brain cooling were a real factor women would be suffering in greater numbers of balding, if not equal to men as they are, and please, quote after me: "Human beings just like men".

Even the annoying "masturbation theory" has more basis in facts than this stupid cooling non-sense. At least there you have loss of zinc and other minerals(in ejaculation) that can create imbalance of minerals.

 

[freakout]

"brain cooling" (theory) mentioned one too many times ... If brain cooling were a real factor women would be suffering in greater numbers of balding ...

Perhaps but we can still throw in the androgen factor to account for the difference in men and women.

Such a theory can only apply to frontal scalp hairloss - Norwood Type 5A - not the entire vertex scalp since only the frontal scalp reflects internal cerebral temperature.

Even so, if there is any credit to this "brain cooling" theory, such an occurence could only only a response to an adverse condition - that of a tendency for the cerebral tissues to overheat.

The primary coolant of the brain is blood circulation. Therefore such a theory could be the result of poor blood circulation.

 

[freakout]

We already know that hair follicle growth characteristics is recipient or site dominated and we also have this notion that body hair growth is direcly induced by androgens.

The truth is body hair growth is only associated with increased androgen production.

The results of the mouse experiment where biopsies of the donor scalp which include complete pilosebaceous units where regrowth from vellus to terminal was achieved suggests that the root cause of male pattern baldness is being induced from outside the pilosebacous unit.

 

[Bryan]

After seeing "brain cooling" mentioned one too many times I just have to say this:

Anybody who thinks brain cooling has any reason behind it is a sexist misogynistic pig, I am sorry to say. If brain cooling were a real factor women would be suffering in greater numbers of balding, if not equal to men as they are, and please, quote after me: "Human beings just like men".

I have no idea why you have so much trouble with the "brain-cooling" theory. I think it makes as much sense as any other theory for the evolution of male pattern baldness. It currently has less effect on women for the simple and obvious reason that androgen levels are a very obvious factor in its evolutionary development. I think as the eons go by, balding will gradually have more and more of an effect on women, just as it does on female stumptailed macaques.

 

[S Foote.]

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:

If what you say is true, then the male pattern baldness follicles in the immuno-mouse study would not have regrown.

According to the direct effect theory, everything was present in those transplanted male pattern baldness follicles to maintain them in that condition. And more than enough androgens in the mice (again according to the direct sensitivity claim).

http://www.uphs.upenn.edu/dermatol/facu ... ecLipo.pdf



The topical delivery of transgenes to hair follicles is an attractive
approach for treating disorders of the skin and hair. The hair follicle
contains epithelial stem cells, which cyclically regenerate the lower
follicle1,2, and in times of wounding, repopulate the epidermis as
well3. At the onset of each new growing stage (called anagen), stem
cells in the bulge area of the hair follicle proliferate and give rise to
progenitor (matrix) cells that subsequently generate the hair shaft
and its surrounding layers4. The properties of the matrix cells are
established at anagen onset and determine the characteristics of the
new hair. For example, the number of matrix cells correlates with the
size of the new hair5, and the pigmentation of the hair depends on
the presence of melanin in the matrix cells6. Therefore, gene-based
therapies targeted to follicle progenitor cells at anagen onset could
alter the phenotype of the new hair follicle, and its associated hair.

Has this theoretical treatment grown any hair on the human male pattern baldness scalp yet?

 

[freakout]

i know there is a transplant procedure wherein large sections of the scalp at the back are transplanted to the front. Obviously, the front scalp has to be moved to the back.

Does anyone know of such a case and can verify that the bald or balding hairs continued to lose or regrow some hair?

What ever the results of such a case, it could support or throw a hammer on the mouse experiment.

 

[S Foote.]

Has this theoretical treatment grown any hair on the human male pattern baldness scalp yet?

Please understand....I lean more to the "non-direct effect" side....

but, questions must be answered....

there is no light without darkness....

and since no one else is asking you questions.... :whistle:

then I will!

In regards to your question...please check current clinical stage of Follica's approach. It is my understanding that the "wounding" aspect of their treatment is of central importance...however, a topical treatment is an option that, perhaps, may help results. (wounding by a "medical device" speeds FDA approval from my understanding...please correct me if I am wrong!)

I also ran into this study:

http://www.ncbi.nlm.nih.gov/pmc/article ... =pmcentrez

This study speaks to some of the issues we are exploring.....

In this report, we address these key questions in the unperturbed in vivo confines of the normal hair cycle, as well as in response to injury. In so doing, we unearth surprising and dynamic features of the HF-SC niche and its progeny. First, we show that during anagen, the upper ORS remains slow-cycling, like their SC predecessors, while lower ORS cells cycle more rapidly. Moreover, slow-cycling ORS cells survive catagen and contribute mightily to both HG and a new bulge: in fact, they become the main source of SCs used during the next hair cycle. Lacking a DP, the initial bulge ceases to play a major role in homeostasis but can respond to injury. Finally and perhaps most surprisingly, some actively cycling lower ORS cells not only survive catagen, but also home back to the bulge. Like their upper ORS predecessors, these cells retain many HF-SC markers. However, they irreversibly lose their ability to proliferate in normal homeostasis or upon wounding. Instead, they function decisively in hair anchorage during the resting phase and in providing the quiescent signaling cues that control the hair cycle. Our findings define a point along the ORS where cells lose stemness and become irreversibly fated to differentiate or die, and illuminate how downstream SC progeny can provide negative feedback to the niche and restrict SC self-renewal and tissue formation.

Could this help explain where the "negative" growth factors, influenced by androgens "in" the follicle occur, and, how their damaging effects can influence not only the current follicle.......but the "next one" as well?

Anyway.....

what are your thoughts on the above study?

And how does your theory work with it?

Thanks for your interest and the links.

What i suggest is that there are two things going on when it comes to hair growth. There is the normal hair cycle, and the mechanism of contact inhibition. I dont think that the hair cycle in itself is the problem in male pattern baldness, i think the anagen phase is switched off early by external pressure, then this modifies the other phases of the cycle. I think if you change the external pressure, the hair cycle can sort itself out.

My concern with the hair multiplication and cell/genetic manipulation experiments, is that these are not going to get around normal contact inhibition, if this is the problem in male pattern baldness.

No one knows much about the pathways involved in contact inhibition, only that this is a basic reaction to cell division and tissue growth in-vivo. This prevents tissue growth from invading the space of other tissues, and all normal cells react to contact inhibition of growth. The central characteristics of cancer cells is they lose this reaction, and this is how they cause damage to healthy tissues.

We do know that the Wnt's pathway, b-catenin, and TGF beta-1 are linked to the contact inhibition process, and these factors have been suggested as relevant in male pattern baldness. Fuchs did a mouse study where she manipulated Wnt's and b-catenin, and grew significant amounts of hair. The problem was the tumor developement that went with it.

http://www.hhmi.org/fuchs/index.html


In my opinion, there could be ways that HM could work, a wounding process should help because it is thought that contact inhibition is "relaxed" because of injury to allow better healing. Some proposed procedures claim a matrix of some kind to help in tissue growth, basicaly a "mould" that allows tissue growth.

I think there could be easier ways forward with research shifted to the surrounding tissue, and maybe this currect HM research will reach that conclusion?

 

[S Foote.]

i know there is a transplant procedure wherein large sections of the scalp at the back are transplanted to the front. Obviously, the front scalp has to be moved to the back.

Does anyone know of such a case and can verify that the bald or balding hairs continued to lose or regrow some hair?

What ever the results of such a case, it could support or throw a hammer on the mouse experiment.

I think the "flap" grafts were dropped because of tissue survival problems. Having had four scalp reductions 30 years ago, i can tell you that over time, the hair recceded back to where it started from. I am sure if genuine experiments were done, this would be proven to be the norm.

 

[Bryan]

I'll tell everybody a true story, just as a demonstration of the ridiculous lengths to which Stephen Foote will go: a few years ago, I asked him to explain why it is that excised scalp hair follicles show the same response to androgens in vitro that they do in vivo. Sitting there in a petri dish in a laboratory, they certainly aren't subjected to supposed "contact inhibition", so why would androgens still suppress their growth??

The answer he gave me (I have no idea if he said this with a straight face, or if he was incredibly embarrassed and red-faced while typing it) was that the "contact inhibition" caused the hair follicles to become sensitive (apparently permanently?) to androgens!!! Seriously, that's the actual answer he gave me!! :mrgreen:

I think this is a good example of the extent to which he'll go, just to try to prove his own eccentric theory about "contact inhibition".

 

[S Foote.]

I'll tell everybody a true story, just as a demonstration of the ridiculous lengths to which Stephen Foote will go: a few years ago, I asked him to explain why it is that excised scalp hair follicles show the same response to androgens in vitro that they do in vivo. Sitting there in a petri dish in a laboratory, they certainly aren't subjected to supposed "contact inhibition", so why would androgens still suppress their growth??

The answer he gave me (I have no idea if he said this with a straight face, or if he was incredibly embarrassed and red-faced while typing it) was that the "contact inhibition" caused the hair follicles to become sensitive (apparently permanently?) to androgens!!! Seriously, that's the actual answer he gave me!! :mrgreen:

I think this is a good example of the extent to which he'll go, just to try to prove his own eccentric theory about "contact inhibition".

This kind of outburst is exactly why the smart people on the forums dont take you seriously Bryan.

The in-vitro studies do not reflect what goes on in the body, the immuno mouse study is just the latest nail in the coffin of the relevance of test tube studies. OK, your just to stupid to understand this. People can see your basic stupidity for themselves in this very thread.

I posted a link for you about a study that clearly showed that follicle cells behave very differently in-vivo than they do in-vitro, even before androgens come into it! This was:

"Study of Cell Senescence in Cultured
Primary Balding and Non-Balding
Dermal Papilla Cells
A.W. Bahta
Dermatology (QMUL), London, UK"

Your response was to call this a "pointless" study with no further comment. Pointless just because it didn't agree with you Bryan!

I have posted reactions from scientists to my theory in this thread that prove that i can be taken seriously outside of "internet forums"

Your kind of twisted reasoning can only exist in these forums, and you would be laughed at in the real scientific community, as Dr Yechiels reaction to you proved.

So rant away Bryan. no one who knows about science is listening to you.

 

[freakout]

I Broke the Mystery of Male Pattern Baldness

I think the "flap" grafts were dropped because of tissue survival problems. Having had four scalp reductions 30 years ago, i can tell you that over time, the hair recceded back to where it started from. I am sure if genuine experiments were done, this would be proven to be the norm.

Thanks. Would you consider scalp reduction 'pulling the recipient site to the donor site or 'pulling a donor to the recipient site? Tough question, huh?. :woot:

The reason I brought up the 'flap' grafts is because I was particularly interested on transplant of the frontal scalp to back. If my theories are correct, they should regrow hair.

 

[S Foote.]

Re: I Broke the Mystery of Male Pattern Baldness

I think the "flap" grafts were dropped because of tissue survival problems. Having had four scalp reductions 30 years ago, i can tell you that over time, the hair recceded back to where it started from. I am sure if genuine experiments were done, this would be proven to be the norm.

Thanks. Would you consider scalp reduction 'pulling the recipient site to the donor site or 'pulling a donor to the recipient site? Tough question, huh?. :woot:

The reason I brought up the 'flap' grafts is because I was particularly interested on transplant of the frontal scalp to back. If my theories are correct, they should regrow hair.

They are as you describe, "pulling the donor to the recipient site."

Mine were done by a top clinic at the time, and the whole scalp was loosened to avoid what people refered to as "stretch back". Even so over time, the hair moved "up" receeded back to its starting position.

I would be interested in why you think you would get regrowth in the procedure you describe?

 

[freakout]

I would be interested in why you think you would get regrowth in the procedure you describe?

The mice experiment came up as a surprise to the researchers. The original intention was to develop more efficient transplant proceduces if i read it right.

The transplanted follicles are contained in biopsies of the scalp of 28 men 11 women all of which regrew hair which labels them as scalp transplants - not just hair follicles transplants.

When they regrew hair, it suggested that nothing was wrong within the pilosesbaeous units; that by merely removing them from the human scalp and transplanting them elsewhere, the units will regrow hair normally - as if nothing was wrong just days before.

We also know that there are several indications that hair growth characteristics are determine by the recipient site - Donor Dominance Takes a Bow. In this case, a follicle was transplanted.

However, if that were true, the follicles should not have regrown hair several inches on the mice since mice maintain hair length just a few centimeters long. However, it suggested that hair growth characteristics is determine by the pilosebeceous units.

Regardless of the donor or recipient site dominance assertions, the outcome of the mice experiments suggested that the root cause of male pattern baldness is being induced from OUTSIDE the pilosebeceous units.

The association of male pattern baldness with several serious diseases and conditions supports the suggestion that male pattern baldness is being induced from OUTSIDE the pilosebeceous units. It is also obvious that whatever is causing male pattern baldness, it has no effect on the 'horseshoe' area (back and sides of the head).

Therefore, if the hair folicles are capable of fixing themselves, as shown in the mice experiments, transplanting balding scalp to the 'horseshoe' area should allow them to fix themselves as well.

However, only an actual procedure can confirm this.

These are the reasons why I never read any argument or study which tend to focus on the scalp particularly within the pilosebeceous units or the follicles.