Gadgetine

Understanding Androgenetic Alopecia

S Foote.

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I really care about better male pattern baldness treatments.
Contrary to your beliefs, I don't think a one off research paper from 2002 done in vivo using mice is the most important work in the field.
1. Mice regen/remodel quickly including the specialized structures in skin, humans don't.
2. Not paying thirty bucks to discuss the contents of the full paper with you.
3. Do it in vivo in human skin as it seems just about anything, short of killing it, done to a mouse grows freaking hair.

Let me elaborate here.

Yes you are right to say that mouse studies don't mean anything when it comes to human hair growth. But the important thing about this particular study is that it used transplanted human hair follicles. All the mouse tissue did was give them life support.

So the important thing is to identify why these human follicles don't behave in this tissue, as they do in normal human transplantation studies?

This is obviously because of a reason outside of the transplanted follicles, and not within them as is the usual claim.

So we need to know what is the physical difference in the surrounding tissue, compared to human tissue.

I think it is important to do this experiment again with variations. Body hair samples should be used as well, and the DHT levels in the mice should be set at the high end of those in human male pattern baldness scalp. Tissue biopsies should be taken to study the interface with the human and mouse tissue, looking for fibrosis and other relevant conditions and substances.

Again any valid explanation here has to show scientific parsimony. Remember all the human follicles enlarged. Even those that are not considered to be affected at all by androgens through whatever pathway. And the end result was that "ALL" of the human follicles reached the same size.

If it is to be claimed that these male pattern baldness follicles enlarged because of the lack of immunology itself, then parsimony dictates that this should also apply to the androgen "neutral" follicles as well. So why don't we see reports of over enlarged follicles in cases of human immune deficiency? There are no reports of kids born with no immune systems who have to live in isolation, having excess hair growth anywhere on their bodies.

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So you are convinced by a mouse study.. First let me tell you that in humans in vivo this approach doesn't work. It doesn't mind where you will take your miniaturized hair follicle and transplant it on your ***, hand, back or chest. It won't magically regrow. We ain't mice S. Foote. Anyway lets break that study up a bit;

1. If you have read that study you know that Van Neste contradicts this study (1.)
2.
3. The most important one by far; They might for instance have an excellent autophagy or macrophage system or something else that makes this possible. If we were the same as mice we would be happy inducing de-novo morphogenesis of hair follicles currently through wounding. But hey we ain't mice.

The process starts in Androgenetic Alopecia when androgens bind to the androgen receptors in the dermal papilla cells. Everything what happens "before" that process is irrelevant to the pathology of Androgenetic Alopecia, simple as that.




1.Van Neste D. The use of scalp grafts onto nude mice as a
model for human hair growth: is there something new for
hair growth drug screen programs? In: Maibach HI, editor.
Dermatologic research techniques. Boca Raton (FL): CRC
Press; 1996. p. 37-49.

Well of course it doesn't work in humans, that's the whole point! We need to find out the precise reasons why.

I would like to read the Van Neste study referenced in full if anyone can provide a link. I cannot comment on your take on it without the proper context of your claims.

In the particular strain of nude mice used, did the balding follicles also enlarge initially then miniaturise in response to increased androgens? Were non male pattern baldness follicles also used as a comparison, as in the other study?

Because if not then you are just not comparing like for like. Also any differences in the strains of mice here, could narrow down the reasons for any different hair growth responses.

Quote:

"The process starts in Androgenetic Alopecia when androgens bind to the androgen receptors in the dermal papilla cells."

So please explain why it is that it can take years before we see any effect of this on hair growth? Such a long delayed response in directly hormone targeted cells is just not recognised. So how can this happen through any recognised mechanism?
 

Swoop

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Quote:

"The process starts in Androgenetic Alopecia when androgens bind to the androgen receptors in the dermal papilla cells."

So please explain why it is that it can take years before we see any effect of this on hair growth? Such a long delayed response in directly hormone targeted cells is just not recognised. So how can this happen through any recognised mechanism?

You make many of these quotes.. You really have much to learn about the human body, hair follicle, Androgenetic Alopecia, and cellular function in general. Nonetheless, if you would have read everything of me in detail and would go over actual literature you would understand how that is possible. The thing is you preach your bs "theory" from 1995 that says enough for me. Try to actually read full journals and studies and have an open mind to everything. You'll be amazed how much there is to learn.
 

S Foote.

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You make many of these quotes.. You really have much to learn about the human body, hair follicle, Androgenetic Alopecia, and cellular function in general. Nonetheless, if you would have read everything of me in detail and would go over actual literature you would understand how that is possible. The thing is you preach your bs "theory" from 1995 that says enough for me. Try to actually read full journals and studies and have an open mind to everything. You'll be amazed how much there is to learn.

Lets just go to the simple bottom line here.

So androgens cause male pattern baldness directly through internal androgen receptors in susceptible follicles. This is despite the fact that the time frame goes against everything we know about direct hormone actions, and what everyone on these forums can see for themselves.

Also despite such an action being easy to treat, in over sixty years of the persistence of this notion we still have no effective treatments. Companies have come and gone over the years that have tried to develop treatments based on this, only to fold when the funding gets pulled. The money tells the real story here.

In real terms to explain the actual observations, it is necessary to add on so many patches and magical mechanisms to this it defies all scientific principles. Even the most die hard supporter of this notion, should by now be starting to question the assumptions it is based on. But still some people persist.

I think we are just going to have to agree to disagree.

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Yeah puberty and increased androgen levels. It then takes around ten years on average for most peoples male pattern baldness follicles to realise their directly androgen responsive.
 

bushbush

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Lets just go to the simple bottom line here.

So androgens cause male pattern baldness directly through internal androgen receptors in susceptible follicles.

Not necessarily, according to the PGD2 literature.

In real terms to explain the actual observations, it is necessary to add on so many patches and magical mechanisms to this it defies all scientific principles. Even the most die hard supporter of this notion, should by now be starting to question the assumptions it is based on. But still some people persist.

"Magical mechanisms" are those without evidence. Submit your theory for publication and go through peer review in a respected journal to see how it stands up. Until then, they are unsubstantiated musings on a message board with less credibility than the very studies you criticize. A true follower of the scientific method or "principles" would have no issue in doing so.

Yeah puberty and increased androgen levels. It then takes around ten years on average for most peoples male pattern baldness follicles to realise their directly androgen responsive.

You missed the point. From the onset of puberty, hormone mediated changes such as the development of secondary sexual characteristics occur slowly, which to a casual observer might appear to be "delayed". This is another simple example of what you claim is 'just not recognised'.
 

Swoop

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Lets just go to the simple bottom line here.

So androgens cause male pattern baldness directly through internal androgen receptors in susceptible follicles. This is despite the fact that the time frame goes against everything we know about direct hormone actions, and what everyone on these forums can see for themselves.

Also despite such an action being easy to treat, in over sixty years of the persistence of this notion we still have no effective treatments. Companies have come and gone over the years that have tried to develop treatments based on this, only to fold when the funding gets pulled. The money tells the real story here.

In real terms to explain the actual observations, it is necessary to add on so many patches and magical mechanisms to this it defies all scientific principles. Even the most die hard supporter of this notion, should by now be starting to question the assumptions it is based on. But still some people persist.

I think we are just going to have to agree to disagree.

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Yeah puberty and increased androgen levels. It then takes around ten years on average for most peoples male pattern baldness follicles to realise their directly androgen responsive.

You still didn't read my story. It shows why you hold a closed mind and know absolutely nothing. You have much to learn, that's for sure. Now stay out of this topic and actually ask intelligent questions before I'll respond to you. Let me tell you that your "theory" is absurd. Actually put some effort into understanding something and go over literature and papers with a objective open mind. If you would have , you wouldn't be preaching your bs "theory".

S. Foote in 1995 ;

Hair growth and the fluid factor.

Foote SI.
Abstract


It is accepted that the detailed mechanisms of changes in human hair growth patterns are poorly understood. It is this uncertainty that has encouraged many charlatans to operate in this area. From my perspective as an engineer, however, there is a simple mechanism that makes sense of these changes. I suggest this mechanism is closely connected with the evolution and function of hair. The fact that the presence of this mechanism can be demonstrated in the male pattern baldness scenario, raises a number of serious questions relating to fundamental physiology and the mechanisms of some serious diseases. As an amateur, it is difficult for me to gain access to up-to-date research data, so my references are derived from textbooks. I would therefore welcome comments from professionals who are involved in the areas indicated in this paper.

You are an amateur and you will stay an amateur if you don't gain access to up-to date research data and put effort into understanding. For now you are frozen in time for 20 years. Read my story, if you don't understand the definitions look them up so you will understand. I'm not here to describe some fabricated "theory" by me but a consensus laid out by highly skilled academics and researchers from the latest time who are implicated in researching Androgenetic Alopecia. Let me tell you that if you will read everything and understand everything you wouldn't be asking me such questions like you do now, frankly it will also give you all your answers for the oberservations in Androgenetic Alopecia. Cheers.
 

LayZ

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You still didn't read my story...

I was going to reply to Foote directly, but as you say above, he either did not read or rejected out of hand all that was posted prior in this thread.

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I repeat, Foote ignores or rejects out of hand all that was posted or all that was posted prior in this thread.

And thank you Swoop and bushbush for providing actual stimulating conversation concerning the recent consensus of how male pattern baldness researchers actually approach the obstacles in front of hairloss sufferers today
 

Swoop

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@LayZ no problem man, you too thanks.

________________________________________________________


You guys know I mentioned senescent cells can secrete anti-inflammatory factors right? I quoted this;



I already showed that in fibroblasts and epithelial cells SASP is accompanied by a increase of 40-80 factors. I’ll name a few, IL-6, IL-8, IL-1, GM-CSF, MCP-3, MMP-1, MMP-3 etc (1)


Now this study says the following ( http://link.springer.com/content/pdf/10.1007%2Fs00018-014-1691-3.pdf) ;

Proteases, such as matrix metalloproteinases (MMPs) and collagenases, secreted by senescent cells are able to cause degradation of the extracellular matrix (ECM) [90– 92]. ECM remodeling is an important mechanism in the regulation of cell differentiation [93], maintenance of stem cells niches [94], angiogenesis [95], bone remodeling [96] and wound healing [97]. Therefore, it is not difficult to envision how ECM destruction can compromise the functional integrity of the surrounding tissue, promoting disease.

Back to the table with differentially expressed genes in Androgenetic Alopecia;

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4164265/table/T1/?report=objectonly

TIMP metallopeptidase inhibitor 3 = expressed 4.29 fold.


This gene belongs to the tissue inhibitor of metalloproteinases gene family. The proteins encoded by this gene family are inhibitors of the matrix metalloproteinases, a group of peptidases involved in degradation of the extracellular matrix (ECM)


Nonetheless, I recommend to read this study a paper from 2014 about senescence;

http://link.springer.com/content/pdf/10.1007%2Fs00018-014-1691-3.pdf


strategies.jpg








 

S Foote.

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You still didn't read my story. It shows why you hold a closed mind and know absolutely nothing. You have much to learn, that's for sure. Now stay out of this topic and actually ask intelligent questions before I'll respond to you. Let me tell you that your "theory" is absurd. Actually put some effort into understanding something and go over literature and papers with a objective open mind. If you would have , you wouldn't be preaching your bs "theory".

S. Foote in 1995 ;



You are an amateur and you will stay an amateur if you don't gain access to up-to date research data and put effort into understanding. For now you are frozen in time for 20 years. Read my story, if you don't understand the definitions look them up so you will understand. I'm not here to describe some fabricated "theory" by me but a consensus laid out by highly skilled academics and researchers from the latest time who are implicated in researching Androgenetic Alopecia. Let me tell you that if you will read everything and understand everything you wouldn't be asking me such questions like you do now, frankly it will also give you all your answers for the oberservations in Androgenetic Alopecia. Cheers.

First I am not an amateur, I have over 40 years experience of real world hands on science in my own field.

Secondly, I have read the posts in this thread and I see nothing new. The veterans on the forums are aware that every once in a while, we get a new science groupie posting studies as if it gives them some kind of personal authority.

These people use a lot of scientific terminology that has very little substance, and never reaches any definite conclusions. One sure give away is they never actually try to explain anything, and if anyone dares to question their authority with genuine scientific points, they just get flamed.

You are more than welcome to your cosy self indulgent thread.
 

Swoop

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First I am not an amateur, I have over 40 years experience of real world hands on science in my own field.

Secondly, I have read the posts in this thread and I see nothing new. The veterans on the forums are aware that every once in a while, we get a new science groupie posting studies as if it gives them some kind of personal authority.

These people use a lot of scientific terminology that has very little substance, and never reaches any definite conclusions. One sure give away is they never actually try to explain anything, and if anyone dares to question their authority with genuine scientific points, they just get flamed.

You are more than welcome to your cosy self indulgent thread.

Yes you are an amateur. You are a guy full of ignorance that is what you are. I'm not a authority i'm delivering the consensus of several researchers for the people here. I'm not taking any credit for what I propose here, i'm just translating it in a big picture for the guys on here. You think you know it all but let me tell you, you as an engineer know totally nothing about biology. Now do me a pleasure and go back to your fantasy topic and theory from 1995.
 

Armando Jose

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Yes you are an amateur. You are a guy full of ignorance that is what you are..

Please don't be so rude with him,....,
I like people with own ideas, for me Dr. Saboreaud was important, in the first decades of past century ;)
 

maher

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Armando is right. Guys, be respectful. Although I don't support S Foote hypothesis, I find it kinda fascinating,
 

LayZ

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Don't be rude to Foote...

This guy thinks he's the Alfred Wegener of Androgenetic Alopecia...
He ain't.
Yeah, he read the thread, nothing new.
He found the most important study! Human hair, from balding and non balding follicles grow big in mice that don't reject said hair!
'Cept if he read page 2 he would have seen the link to the peer reviewed paper in Cell that demonstrated mice repopulate dpc's and the sheath with with viable cells and regrow follicles...
Don't say it's immune related to guy with 40 years in an unrelated field!
'Cept that research outta Spain demonstrated that when macrophages aren't killing invaders, like a human hair stuck in a mouse, they then do crap like help grow hair.
It's in the follicle or outside the follicle says Occam's ham fist!
That's a false dichotomy, tool of the self indulgent. What Androgenetic Alopecia researcher today believes that a hair follicle exists in isolation w/o interaction with the surrounding tissue.
I could go on and on and on.
Do not tell me to be respectful to this guy.

I may wander over to his threads and start jacking just like he did here.
 

Ventures

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Swoop what do you think about this:



  • less AR sites located in donor hair follicles
  • less DHT follicular production compared to hair follicles located at front and top of the head
  • increased blood flow/nutrient and oxygen supply due to occipital muscle
  • other yet unknown factors obviulsy connected to its location on scalp, I found paper that suggests that even sebaceous glands on top of the head are bigger than those located at donor region. Sebaceous glands squeeze hair follicles and shafts causing mechanical degradation/miniaturisation

There is interesting article which
suggests that androgen receptors become active under low oxygen environments, which is a much more logical explanation than extra androgen receptors being located ONLY in the EXACT shape of the galea.

http://www.ncbi.nlm.nih.gov/pubmed/22266320

Hypoxia and the androgen receptor (AR) play important roles in the development and progression of prostate cancer. In this study, the combined effects of dihydrotestosterone (DHT) and hypoxia on AR-mediated transactivation were investigated. Hypoxia alone did not induce a detectable ARE-mediated response in the absence of DHT. DHT-induced AR transcriptional activity was dramatically increased by hypoxia or ectopic expression of HIF-1α, as determined by introducing ARE-responsive reporter plasmids into LNCaP prostate cancer cells. The secretion of VEGF was enhanced by the combination of hypoxia and DHT as compared to each treatment alone. These effects were not due to increased expression of the AR or HIF-1α as a result of hypoxia and DHT treatment. These results provide evidence that hypoxia may stimulate as yet unknown factors, which further stimulate AR signal transduction pathways.
 

Swoop

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Swoop what do you think about this:

· less AR sites located in donor hair follicles
· less DHT follicular production compared to hair follicles located at front and top of the head
· increased blood flow/nutrient and oxygen supply due to occipital muscle
· other yet unknown factors obviulsy connected to its location on scalp, I found paper that suggests that even sebaceous glands on top of the head are bigger than those located at donor region. Sebaceous glands squeeze hair follicles and shafts causing mechanical degradation/miniaturisation

There is interesting article which suggests that androgen receptors become active under low oxygen environments, which is a much more logical explanation than extra androgen receptors being located ONLY in the EXACT shape of the galea.
http://www.ncbi.nlm.nih.gov/pubmed/22266320
Hypoxia and the androgen receptor (AR) play important roles in the development and progression of prostate cancer. In this study, the combined effects of dihydrotestosterone (DHT) and hypoxia on AR-mediated transactivation were investigated. Hypoxia alone did not induce a detectable ARE-mediated response in the absence of DHT. DHT-induced AR transcriptional activity was dramatically increased by hypoxia or ectopic expression of HIF-1α, as determined by introducing ARE-responsive reporter plasmids into LNCaP prostate cancer cells. The secretion of VEGF was enhanced by the combination of hypoxia and DHT as compared to each treatment alone. These effects were not due to increased expression of the AR or HIF-1α as a result of hypoxia and DHT treatment. These results provide evidence that hypoxia may stimulate as yet unknown factors, which further stimulate AR signal transduction pathways.


Hey Venture, interesting study. However we can’t really draw conclusions from that study because it is done on LNCap prostate cancer cells. Different cell types, react differently, act differently and have different characteristics . This is even a cancer cell. Let’s assume that it translates to Androgenetic Alopecia though;

- Why do hair follicles stay resistant when transplanted from the occipital scalp to the balding area?

Btw I want to reiterate again that a healthy hair follicle is thriving and needs a hypoxic (low oxygen) environment. Especially the mesenchymal derived dermal papilla cells and many progenitor/stem cells in the hair follicle. Many people don't know this.

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@Ventures, thought I would quickly break down your points also


  • less AR sites located in donor hair follicles

This is true (http://www.ncbi.nlm.nih.gov/pubmed/9496234). Balding dermal papilla cells contain higher androgen receptors than those from non balding scalp. A study also confirmed that genetic variability in the androgen receptor is a prerequisite for the development of early onset Androgenetic Alopecia (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1226186/?report=reader#!po=58.3333). There is way more on this topic, also with 5ar2 evidence. Men also have 7x less aromatase in scalp than women. Polygenic inheritance.. I'll write a post later about this all in the future if you would like.



  • increased blood flow/nutrient and oxygen supply due to occipital muscle


Many people want to believe this. People are massaging their Galea thinking that is the problem. Thinking they will make it more loose and blood flow will restore to their hair follicles. However what people need to understand that the micro environment of the hair follicle communicates with the dermal macro-environment.

cycling.jpg
adipose_tissue.jpg





This is very important to know. In a healthy hair follicle cycle in telogen there is a tremendous decrease of adipose tissue (soft fat tissue) and vascularization. In anagen there is a tremendous increase in adipose tissue and new blood vessel growth. This leads to a thinner dermis in telogen and a thicker dermis in anagen. The morphology of a minitiurized hair follicle is even "worse" than a healthy non-Androgenetic Alopecia telogen hair follicle. Thus it completely logical that there is less blood flow and adipose tissue present in a miniaturized hair follicle. No wonder you have a "tight" thinner scalp in where all the follicles are resting. This all get's regulated through complex signalling. It's true however that there is downstream signalling present in Androgenetic Alopecia, which might affect fibrotic factors to some extent. Again fact is, if you transplant a healthy non-Androgenetic Alopecia hair follicle to a a balding region, the hair follicle happily goes into telogen first before entering anagen with fresh blood vessel growth and new adipose tissue.

Someone who will get back from chemotherapy and lose his hair will suffer too from a thinner, tighter scalp too which has less blood flow and adipose tissue. Same with someone suffering from from extreme telogen effluvium etc.

About sebaceous gland hyperplasia (a result of Androgenetic Alopecia) I'll post later about that, don't really have too much time now! Hope that helps
 

TNTS

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well swoop, if indeed balding areas hair follicles keep growing when transplanted to mice, then it looks like an environmental problem at dermis - extracellular matrix.


But when non balding areas hair follicles transplanted to the balding area, they will keep growing too, so this looks like a stand alone hair follicle problem.


I wonder if wounding during hair transplant has any effects on the second fact
 

Swoop

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well swoop, if indeed balding areas hair follicles keep growing when transplanted to mice, then it looks like an environmental problem at dermis - extracellular matrix.


But when non balding areas hair follicles transplanted to the balding area, they will keep growing too, so this looks like a stand alone hair follicle problem.


I wonder if wounding during hair transplant has any effects on the second fact

True, that would be a logical conclusion. However when you transplant a miniaturized hair follicle on a human to a other location nothing happens, this has been tried numerous times. Yes that study showed a miniaturized hair follicle growing again in mice, however we ain't mice. They even mention this in their study;

Therefore, the existence of an inhibitor factor other than androgens. This could be some other steroid, hormone, cytokine, neuropeptide, or an immunologically related factor

What do you mean exactly with wounding during a hair transplant?
 

S Foote.

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What people really need to understand is that the assumptions made about transplantation, have never been properly tested!

The early studies accepted two possibilities. The survival of large follicles transplanted into the bald area, is either because of internal differences, or external effects caused by the procedure itself.

This is a very important point because the supporters of the traditional direct androgen action idea, quote transplantation as proving this. But the lack of confirmation testing, leaves this question open.

There is certainly no incentive for the proper testing of this question, within the industry itself. Think about this. Transplants have always been sold on the basis that the transplanted hair is different, and resistent to balding. If it was demonstrated that these hairs are not different, and it is the procedure that makes the difference what would happen?

Everone who has ever had a bad transplant procedure, would have have a legal case for misrepresentation. Think about the implications of that?

From the early transplantation studies using large grafts, and the much later experience of repairing these we get some insight.

The early large grafts suffered central hair loss, that looks just like the male pattern baldness process effecting alledged resistent follicles. These large grafts also suffered from a central swelling refered to as cobblestoning. There are so called explainations for these effects, but the time scale of the early studies is against these explainations.

The overall data suggests that the only follicles to survive long term in the male pattern baldness area, are those within scar tissue. This would indicate it is the procedure that makes the difference, and not internal follicle differences. This is also in line with the evolution of procedures towards small grafts.

Whatever any one's opinions, proper testing of this question is possible. Untill this is actually done, people should not just assume the answer here as is often the case in these debates.
 
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