AGA evolved to protect against prostate cancer ! Any comments?

Medications for hair loss
41

» Bryan –
»
» As for the ideas about whether MPB is currently being selected for or
» against, I find the balding female stumptails fact very interesting.

It IS an interesting phenomenon, isn’t it? :slight_smile:

» Like I said, I have a hard time believing that MPB in humans could have
» really evolved in just the male gender from the beginning.

You’ve lost me on that one! Why is it hard for you to believe? Everybody knows that males have higher levels of androgens than females…

» I think this paints a strong picture. I see a trait that may have been
» totally functional & prevalent in both human genders long ago, but now it’s
» being selected against in recent times.

Well, I’m not sure about the part about it being totally functional in BOTH human genders long ago. As I said before, human males have ALWAYS had more androgens than females, including long ago. But I agree that it may be being selected against in modern times.

» This selection has already squeezed it out of most of the female
» (breeding-age) population by a wide margin. And everyone on here knows
» there is at least some steady pressure to squeeze it out of male population
» too.

You may be correct.

.

42

I think balding would be occurring pretty equally in both human genders if it was a functional and fully-developed trait. Nevermind the androgen levels, I’m speaking in terms of the need for the hair to be missing. It wouldn’t be different from one gender to the other. (And there would be no impetus for evolution to “hide” MPB in females because it’s not attractive; it WOULD BE attractive if it was serving any good purpose.)

It’s true that males have more androgens than females. But right now I’m also going bald while my equally-androgen-loaded brother has no MPB at all.

I think in a scenario where baldness is serving a purpose, evolution would probably ramp up the androgen sensitivity in females’ scalps enough to compensate for the different androgen levels and bald them too.

The fact is that right now the female human breeding population has lost essentially all visible signs of MPB. And breeding-age males risk getting knocked down on the pecking order by showing it, both socially and sexually.

Whatever evolution thought about balding in the past, it’s clearly getting rid of balding in humans these days.

43

» I think balding would be occurring pretty equally in both human genders if
» it was a functional and fully-developed trait. Nevermind the androgen
» levels, I’m speaking in terms of the need for the hair to be missing. It
» wouldn’t be different from one gender to the other. (And there would be no
» impetus for evolution to “hide” MPB in females because it’s not attractive;
» it WOULD BE attractive if it was serving any good purpose.)

The irony here is that I think you’re actually making too big a deal out of the brain-cooling theory of MPB! :slight_smile: The “need for hair to be missing” isn’t really THAT big a need, or perhaps (as I’ve already suggested in this thread more than once) we’re still too relatively early in the evolution of balding for it to have spread effectively to females in our own species. One or the other of those reasons (or both) is presumbly the explanation why our females don’t (yet) show the trait more than they do.

» It’s true that males have more androgens than females. But right now I’m
» also going bald while my equally-androgen-loaded brother has no MPB at all.

Maybe in a few more thousands of years, ALL males will be bald, and maybe even many of the females! :slight_smile:

» I think in a scenario where baldness is serving a purpose, evolution would
» probably ramp up the androgen sensitivity in females’ scalps enough to
» compensate for the different androgen levels and bald them too.

EXACTLY!! But it’s probably still early in the process (assuming that the process is still occurring in modern times).

» The fact is that right now the female human breeding population has lost
» essentially all visible signs of MPB. And breeding-age males risk getting
» knocked down on the pecking order by showing it, both socially and
» sexually.
»
» Whatever evolution thought about balding in the past, it’s clearly getting
» rid of balding in humans these days.

Maybe. Maybe not.

.

44

» »»
» Who knows? If the evolutionary pressure toward balding is indeed
» continuing even in modern times, maybe ALL of humanity (including females)
» will eventually be affected by it, in future millenia.
»

lets hope not
» .

45

» » I guess brain-cooling COULD have theoretically been the source of it.
» » I was partly reacting to the idea that it’s still a legit reason for
» » the trait to be continuing now, which I don’t buy.
»
» Ok, that’s good. All I was ever really talking about in the first place
» was just the evolution of balding in the DISTANT PAST. Whether or not the
» evolutionary trend toward balding is still taking place in the current time
» (with much of humanity living in colder climates, and with air
» conditioning) is anybody’s guess.
»
» » But MPB doesn’t seem to be the rule in many of the existing apes, right?
»
» » So is it evolving separately? Why in the stumptailed macaques and the
» » humans but not so much in the others? Would cranial size explain that?
»
»
» Those are all excellent questions, and I don’t know what the correct
» answers are. I find it strange that those questions apparently haven’t
» been addressed in the medical literature on balding, or discussed on
» hairloss sites. One would think that just from the simple standpoint of
» investigating the process of evolution, it would have been a subject of
» great interest among scientists to tabulate just exactly which primates are
» susceptible to balding and which aren’t, and attempt to answer what seems
» to me to be the fundamental question of whether balding evolved
» separately in different primate species, or whether all the balding
» species are descended from a common balding primate ancestor.
»
» BTW, if it does turn out that balding evolved SEPARATELY in certain
» primate species, it seems to me that would be rather powerful evidence in
» favor of the “brain-cooling” hypothesis. After all, what is the
» probability that that would have happened purely by accident in such
» closely-related species?? The one screamingly obvious connection between
» all primates is their more advanced brains, with (presumably) greater heat
» production!! :wink:
»
» » I see MPB as probably just a foul-up now.
» »
» » Maybe it had a legit brain cooling purpose when apes lived 5 million
» » years ago on the African plains.
»
» Which is ALL I’m talking about. I’m making no assumptions at all about
» whether or not the evolutionary pressure toward balding is continuing even
» in modern times.
»
» I think the theory that MPB evolved as a way to help cool the brain is a
» pretty attractive one. It has a certain elegance to it. It has
» that “ring of truth” to it, in my opinion.
»
» » MPB is also MUCH, MUCH less present in females.
»
» I should point out to you here that in stumptailed macaques, females
» experience balding to about the same extent that males do! :wink:
»
» Who knows? If the evolutionary pressure toward balding is indeed
» continuing even in modern times, maybe ALL of humanity (including females)
» will eventually be affected by it, in future millenia.
»
» .

The “hard” experimentation by Cabanac and Brinnel in the paper “beards, baldness and sweat secreation”, was done in response to Falks previous work.

This is outlined here:

http://www.anthro.fsu.edu/people/faculty/falk/radpapweb.htm

The importance of this research is that it clearly demonstrates that the “Hydraulic” changes in androgen related hairgrowth/loss in tissues, predicted by my theory “ARE” happening.

Cabanacs study given existing knowledge, demonstrates the basic physiological changes related to the fluid characteristics in androgen effected tissues.

This is not any indication of “purpose” in evolution, and the “radiator” hypothesis as an explaination does not add up.

If it was important in the evolution of increased brain “processing” for extra scalp cooling, then macaques would be telling us how they feel about their MPB! They would have their own forums!

There are numerous ways our core blood temperature is controled, and lots of bare body area in humans to radiate excess heat from circulating fluids. So why some kind of evolved androgen driven distinction between men and women? Why the range of male hairloss from non to NW7, and the vast differences in rate of MPB over time in different people with or without beard growth?

There is a far more consistant link with such fluid transfer factors, and temperature control in mammals, as i have argued many times before. But thats another story.

The importance of this particular study was to prove the local fluid related androgen driven changes. It is understanding the “mechanisms” that is important, not guesswork about “purpose” that don’t add up.

S Foote

46

» This is not any indication of “purpose” in evolution, and the “radiator”
» hypothesis as an explaination does not add up.
»
» If it was important in the evolution of increased brain “processing” for
» extra scalp cooling, then macaques would be telling us how they feel about
» their MPB! They would have their own forums!

Thanks for sharing that with us, Stephen.

» There are numerous ways our core blood temperature is controled, and lots
» of bare body area in humans to radiate excess heat from circulating fluids.

Yes, but consider that other primates (including stumptailed macaques) are a lot more furry than humans are. Maybe the evolutionary pressure toward balding in macaques was even stronger than it was in humans, for that very reason. In other words, the monkeys had considerably less bare body area for radiating excess heat than we humans did (or do). That would appear to support the observation that they experience balding far more consistently than humans do.

» So why some kind of evolved androgen driven distinction between men and
» women? Why the range of male hairloss from non to NW7, and the vast
» differences in rate of MPB over time in different people with or without
» beard growth?

I’ve already explained that several times in this thread, but being a very patient person, I will explain it yet again: you shouldn’t assume that balding in humans is a fait accompli. I consider balding in humans to be a WORK IN PROGRESS, and it’s not even entirely out of the question that the evolutionary pressure toward balding may no longer be in effect, for the reasons that have been previously suggested.

My own assumption is that balding in humans is still currently in its relatively early stages, which accounts for both the general lack of it in females, and the wide range of its occurrence in males. I further assume that as the eons go by, humans will be more and more consistently and more and more thoroughly affected by it, eventually including females (that’s assuming, of course, that there is indeed a continued evolutionary pressure toward balding, even in modern times).

» There is a far more consistant link with such fluid transfer factors, and
» temperature control in mammals, as i have argued many times before. But
» thats another story.

And that “other story” has been soundly refuted by the Nordstrom study, and numerous other considerations. Time to move on, Stephen. Find something more productive to do in your spare time.

.

47

I think baldness is linked with the ectodysplasin genes going along with a variant of the androgen receptor gene in the first trimester in fetal development as the skin grows up over the top of the fetus’es head, encoding the inensity of androgen-receptor response and setting up the grain of the hair, and shape of the future hippocratic wreath. As a man ages, and repeat mutations in the receptor-gene increasingly assert themselves, the higher the downstream responses to the situation are (baldness in all its manifestations ensue).

Even though Gorilla’s dont typically bald, their foreheads get a bit more prominent as they age, displaying wisdom and social status amongst the group. We genetically KNOW that mice who are better in mazes (the smarter mice) are more likely to have sebaceous gland hyperplasia and loss of hair, so baldness might be a way to show you are advanced and smart in the group also. Cooling of the brain in the very hot African past is also another very viable idea as the males who perhaps weren’t so physically dominant had to think much more to get by, making their developing brains work overtime to make it. Perhaps the weaker primates needed more androgenic stimuli to be competitive and the hypersensitivity of their androgen receptor’s could have helped in this. WE KNOW THAT A VARIANT OF THE ANDROGEN RECEPTOR GENE IS THE ONE CONCLUSIVE GENETIC LINK TO BALDNESS. A South Korean Study, linked I think here at hairsite, showed that there is no difference in alpha five reductase-associated genes and common baldness…so we can rule out that your scalp is doing something different in terms of alpha five reductase. Its the receptor. These are possible evolutionary pressures, but it doesn’t mean any of them are right.

When androgen is uptaken, different genes are activated. It DOES NOT GO LIKE THIS: DHT uptaken at receptor, DKK-1 released from dermal papilla (and DKK-1 kills some keratinocytes in the infidula and the first inflammation in baldness is seen, drum roll please, in the infidula—inviting an immuno response against dead cells in the body but I digress).

IT GOES LIKE THIS: DHT uptaken at receptor, receptor then sees certain androgenic marker genes assert themselves (they even have names for some of these, and soy for instance, actually keeps some of them from expressing themselves while not interefereing with the receptor uptake or blocking the receptor (although over time soy probably does decrease receptor expression if human cell experiments are a good predictor). Then things like DKK-1, thrombospondin, TGF-beta 1, TGF-beta 2, Fiberblast Growth Factor 5, PKC are all upregged in androgenic alopecia subjects, and downstream processes occur.

It may be as easy as stopping one or two of the androgenic marker genes (these things had a mix of numbers and letters like “2G3LH1”) from asserting themselves as to stop baldness. In fact, if certain ones can be made to express themselves downstream of receptor uptake, hair might even like androgens like body hair. Or it could be that just too much male hormone is uptaken over the years as the CAG repeats on the androgen-receptor gene assert themselves and new receptors are made, and alopecia is the result of the body trying to protect itself from cancer in the scalp----or its a evolutionary signal (previously discussed) to start baldness up there to display status, cool the brain, show you are smart, or whatever.

48

more on ectodysplasin and AR genes from older posts----

» > Its known that the variant of the androgen receptor gene is located on
» the
» > x-chromosome and comes from your mother, but the other genes in
» baldness
»
» An ectodysplasin gene (which is located on the X chromosome, near the AR
» gene) has now been linked to MPB. The ectodysplasin signalling system has
» already been shown to be important in hair biology…do a search on Pubmed
» for more details. You’ll be hearing about this study in the lay media
» pretty soon, I’m sure:
»
» J Invest Dermatol. 2008 Apr 3 [Epub ahead of print]
»
» EDA2R Is Associated with Androgenetic Alopecia.
»
» Prodi DA, Pirastu N, Maninchedda G, Sassu A, Picciau A, Palmas MA, Mossa
» A, Persico I, Adamo M, Angius A, Pirastu M.
»
» 1Shardna Life Sciences, Pula, Italy.
»
» Androgenetic alopecia (AGA) is a common heritable polygenic disorder whose
» genetics is not fully understood, even though it seems to be X-linked. We
» carried out an epidemiological survey for AGA on 9,000 people from 8
» isolated villages of a secluded region of Sardinia (Ogliastra), and
» identified a large cohort of affected individuals. We genotyped 200 cases
» and 200 controls (mean kinship 0.001) with the 500k chip array and
» conducted case-control association analysis on the X chromosome. We
» identified Xq11-q12 as strongly associated with AGA. In particular, we
» found that rs1352015 located 8 kb from the EDA2R gene showed the best
» result (P=7.77e(-7)). This region also contains the AR gene, hence we
» tested both genes in 492 cases and 492 controls. We found that the
» non-synonymous SNP rs1385699 on EDA2R gave the best result (P=3.9e(-19))
» whereas rs6152 on the AR gene is less significant (P=4.17e(-12)). Further
» statistical analysis carried out by conditioning each gene to the presence
» of the other showed that the association with EDA2R is independent while
» the association with AR seems to be the result of linkage disequilibrium.
» These results give insight into the pathways involved in AGA etiology.
»
» Journal of Investigative Dermatology advance online publication, 3 April
» 2008;
»
» doi:10.1038/jid.2008.60.
»
» PMID: 18385763 [PubMed - as supplied by publisher]

That link you posted, showing a gene that is statsitically signifigant in baldness, and almost assuredly has a direct influence on it, got me to looking around and I came up with this…

Article

Min Zhang 1, Anna Brancaccio 2, Lorin Weiner 1, Caterina Ectodysplasin regulates pattern formation in the mammalian hair coat Missero 2, Janice L. Brissette 1 *
1Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA
2Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy

email: Janice L. Brissette (janice.brissette@cbrc2.mgh.harvard.edu)

*Correspondence to Janice L. Brissette, Cutaneous Biology Research Center, Massachusetts General Hospital-East, Bldg. 149, 13th St., Charlestown, MA 02129

Funded by:
National Institutes of Health
Cutaneous Biology Research Center through the Massachusetts General Hospital/Shiseido Co. Ltd. Agreement
Italian Telethon Foundation
TIGEM with funding from Regione Campania

Keywords
Eda • tabby • ectodermal dysplasia • ED1 • Edar

Abstract
Summary: develoIn mammalian skin, hair follicles develop at regular intervals and with site-specific morphologies. This process generates distinct patterns of hair, but the mechanisms that establish these patterns remain largely unknown. Here we present evidence of follicular patterning by ectodysplasin-A1 (Eda-A1), a signaling protein necessary for the proper development of hair and other appendages. In transgenic mice, Eda-A1 was targeted to the epithelial compartment of the ping skin. At periodic locations, multiple hair follicles were induced side by side, without any interfollicular space. These follicles grew into the dermis as a fusion and subsequently branched to create discrete stalks and hair bulbs. Thus, at sites where interfollicular skin normally forms, hair follicles developed instead. This result shows that Eda-A1 can regulate basic developmental decisions, as cells were switched from interfollicular to follicular fates. Given these effects, it is likely that Eda-A1 is among the key regulators of pattern formation in the skin. genesis 37:30-37, 2003. © 2003 Wiley-Liss, Inc.

Me again…perhaps this ‘Ectodermal-A1’ gene is the one that makes the decisions as your head skin grows up over your head in fetal development and determines where your most androgen-sensitive hair will be (the shape of your hippocratic wreath), or where your best working androgen-receptors will be (Im basing this on a study I saw that showed androgen receptors in sebaceous glands in male pattern baldness subjects were much better at uptaking androgens that receptors from sweat glands from occipital scalp). A working “guess” is forming anyway in my mind about it. Here is another study showing that ectodysplasin ‘gene’ and the development of the sweat glands (Do you remember how Stephen Foote used to go on about how bald areas of scalp are better at sweating than hairy areas of scalp? Maybe this is a reason why----other than the sweat glands in bald scalp receptor-sites probably have more available testosterone around due to the tiny vellus hairs not having as many androgen receptors available to uptake androgen in a competing sense physically:
[Relationship of ectodysplasin gene signaling with development and regeneration of sweat glands][Article in Chinese]

Zhou G, Li H, Fu X.
Key Research Laboratory of the Wound Repair, the 304th Clinical Department, General Hospital of PLA, Beijing, 100037, P.R. China.

OBJECTIVE: To investigate the expression of ectodysplasin (EDA) gene signaling and its relationship with the development and regeneration of sweat glands. METHODS: The articles concerned in the latest years were extensively reviewed. RESULTS: EDA gene is an important signaling pathway associated with the developmental procedure of sweat glands in early fetal stage. Abnormality or depletion of function in sweat glands partially owed to the defect of EDA gene. CONCLUSION: EDA signaling has its biological significance in inducing development and morphogenesis of sweat glands and in maintaining physiological function of skin. It could be a new approach to repair or regenerate the sweat glands for clinical therapy by regulating the expression of EDA gene.

PMID: 16752854 [PubMed - in process]

Me again (again–LOL)…TAGOHL, I know the sweat glands would at first seem to be unimportant, but they are tissues in the dermis and here we have that same gene again seemingly being involved on an important part of the skin. Loren Pickart has wrote on his site that the hair follicle seems to be the “command center” for skin-remodelling and signalling. I always noticed that women who pluck out their moustaches repeatedly after menopause seemingly have the upper portions of their mouths age terribly after the hair follicles get destroyed from repeatedly pulling them out-----

Post reply

49

» WE KNOW THAT A VARIANT OF THE ANDROGEN
» RECEPTOR GENE IS THE ONE CONCLUSIVE GENETIC LINK TO BALDNESS.
» A South Korean Study, linked I think here at hairsite, showed that
» there is no difference in alpha five reductase-associated
» genes and common baldness…so we can rule out that
» your scalp is doing something different in terms of alpha five reductase.
» Its the receptor.

Sure, but we’re pretty much just treading water as long as we keep focusing on the things which account for the intensity of the androgenic stimulus. We need to understand what accounts for the paradoxical response of body hair follicles and scalp hair follicles to androgens.

.

50

»
»
» Sure, but we’re pretty much just treading water as long as we keep
» focusing on the things which account for the intensity of the
» androgenic stimulus. We need to understand what accounts for the
» paradoxical response of body hair follicles and scalp hair follicles
» to androgens.
»

Bryan,
That could be the androgen-inductible genes that are activated before the ‘alphabet soup’-growth factors get released by the papilla. The AR-uptakes the androgen, and moves to the center of the papilla and it gets read and then certain genes are activated, right?

Perhaps when there has been X-amount of androgenic stimulation, the genes activated -change- here.

If you think about it, occipital scalp hair is where this could be tested with ex-vivo in experimentaion. High hormonal stimulis has been known to make the occipital hairs response change from nothing to bad. The genes in the test tube that change could be identified and we would know which ones either start getting insigated by excessive androgenic uptake or which ones are getting silenced by excessive androgenic uptake. The one’s that “changed” when more androgen is added are the one’s to look at----to see if they can be chemically silenced.

The thing is, is this a defensive mechanism on the part of the body in response to too much androgenic stimulation in hair follicles? Is it protecting us from something? Or is it just too many cag-repeats in the androgen receptor expression just getting too much androgenic uptake to the dermal papilla and the genetic instructions to shrink the hair follicle take place because of too much androgenic stimuli-----much like a steroid users testicles shrink over time because he has too many androgens in the body and the HTPA axis detects he doesn’t need any more?
» .

As far as head hair not liking or being ambivalent about male hormone vs. body hair liking it…that would take changing some dna instructions within the follicle itself, but even before MPB----the head hair didn’t grow because of androgens of course. It never “liked” androgens as opposed to body hair which has to have them to grow.

I’d like to know if head hair has more androgen receptor expression than body hair???

If head hair has alot more androgen receptors, perhas if one gave body hair enough androgen something similar would happen to it?

51

Bryan wrote:

“I’ve already explained that several times in this thread, but being a very patient person, I will explain it yet again: you shouldn’t assume that balding in humans is a fait accompli. I consider balding in humans to be a WORK IN PROGRESS, and it’s not even entirely out of the question that the evolutionary pressure toward balding may no longer be in effect, for the reasons that have been previously suggested.”

But you miss the whole point of the radiator theory as outlined by Falk in the link i provided Bryan.

Falk hypothesised that it was necessary for extra brain cooling to evolve “BEFORE” the development of the human brain could happen! It was the complex fluid system around the brain that first allowed human brain size to evolve (according to Falks hypothesis).

Falk links human brain size with the prior development of increased numbers of emissary veins. Quote:

“emissary veins veins that pass through apertures (foramina) in the cranial wall and establish communication between the sinuses and veins inside the braincase and the veins external to it.”

It is by this “Hydraulic” connection that heat is removed from the brain into the general circulation.

So if it was important that the “radiator” be the MPB area, both sexes would have no hair in the MPB area from birth. The “plumbings” the same in both sexes, so obviously the “position” of the radiator is not important and nothing to do with MPB in humans.

The other factor here is basic common sense.

Lets say it was important to have a bare skin radiator close to the evolving human brain because of hot conditions. The hottest conditions are when the sun is directly overhead. As bipeds this would directly heat up the bald top of the head (radiators have to be cooler than the fluid flowing through them to work not hotter!). So if scalp hair loss did evolve as a radiator, we would have hair on the top to protect the top of the head from direct heating, and no hair at the sides and back to act as the radiator.

Just the opposite to the MPB situation.

Bryan wrote:

“And that “other story” has been soundly refuted by the Nordstrom study, and numerous other considerations. Time to move on, Stephen. Find something more productive to do in your spare time.”

You have yet to produce any genuine “science” that refutes my theory Bryan. Just trying to claim you have over and over does not make it so!

The link with androgen related hair growth/loss, and sweating capacity according to my theory is described in “The Hydraulic Dermal Model” section here for those unaware of my theory.

http://www.hairsite2.com/library/abst-167.htm

Benji a question?

You post studies claiming genetic differences between MPB follicles and others. Have you got any references for any studies that find such differences in scalp follicles “BEFORE” mpb sets in?

Because if not, you are looking at the wreakage of a plane crash, finding that something is different “now”, then claiming that must be what caused the crash!

What evidence i know of clearly shows when “now” normal but “future” MPB follicles in macaques are soaked in androgens, nothing happens!

Bryan claims that MPB follicles have to be exposed to androgens for a period of time before they respond (this must be up to a period of years to be true). Hence this initial non reaction of future MPB follicles to androgens.

Big problem with this guesswork!

Every new hair cycle, the new follicle cells develope from bulge stem cells. Stem cells by definition are no “different” from each other, so where does this alledged “difference” in follicle makeup come from?

This also proves Bryans claim wrong, because if follicles need time to respond to androgens as he says, we would have normal growth from each “new” anagen follicle for a period, before androgens could then “directly” cause MPB. We all know this doesn’t happen!

So how do you figure these facts into the direct theory?

S Foote.

52

» » Benji a question?
»
» You post studies claiming genetic differences between MPB follicles and
» others. Have you got any references for any studies that find such
» differences in scalp follicles “BEFORE” mpb sets in? Its actually pretty simple Stephen, ex vivo hair follicles can only be cultivated for about two weeks, and even soaking them in androgens for this period isn’t enought time for them to start exhibiting mpb-hair follicle characteristics. Most men dont go immediately bald at 13 years age Stephen, when they have the first big rush of post-pubescent testosterone…but about 20% of men are balding at age 20 and several men on the forums will attest to their hairlines starting the process by 16, 17, and 18. Perhaps Stephen IF HAIR IS IN THE ANAGEN PHASE AT 13, IT WILL STAY IN ANAGEN AND FUFILL ITS CURRENT 3-6 YEAR CYCLE, and then the new hair that replaces it–being incubated in the body from the telogen, catagen, and early stages of anagen and being built from stem cells that are “soaked” in adrogens, will exhibit MPB characteristics.
LIKE I SAID IN MY POST, as we age the CAG repeat mutations become more evident and “worse”, and If I were a betting man, I’d bet that a man of 30 is exhibiting more androgen-receptor expression in his frontal hair follicles than he is at 14. » In fact Stephen, we KNOW that frontal hair follicles have more androgen receptors than occipital follicles, and we also KNOW that if occipital follicles are given enough androgens, they will respond negatively to them. »

Because if not, you are looking at the wreakage of a plane crash, finding
» that something is different “now”, then claiming that must be what caused
» the crash! This is a poor analogy Stephen. MPB-follicles, when given androgen in experiments, see their dermal papillas emit more negative growth factors (tgf beta, dkk1, pkc, thrombospondin, fgf5, etc) than hair follicles from the back and sides of the head, which emit more positive growth factors. So they still function, but differently…they recieve androgen and want to go into telogen, instead of being relatively unaffected by them. If they recieve no androgen either on a SCID mouse’s back or a test tube, they grow as well as other follicles. I wouldn’t call this a “car wreck” because this car can be just fine and remake itself as well as the other cars on the car lot, if you simply remove male hormone.»

» What evidence i know of clearly shows when “now” normal but “future” MPB
» follicles in macaques are soaked in androgens, nothing happens! That is one experiment, other experiments with even occipital hair shows that even hair in the wreath can become sensitive to androgens if they get enough of them. How many experiments have been done with pre-pubertal hair follicles though Stephen, really? This was one experiment with pre-pubertal stumptailed macaque head hair, and its result is intriguing, but has it been replicated even once? Maybe they didn’t seed the hairs with androgen receptors like they should have, maybe they didn’t give them enough androgens, maybe alpha five reductase enzymes were lost in cultivation (a problem if things aren’t done extremely carefully from what I understand) and the T alone wasn’t enough androgenic stimulation to make baldness happen as a result (DHT has a five times slower dissassociation rate from an androgen receptor as T has). »

» Bryan claims that MPB follicles have to be exposed to androgens for a
» period of time before they respond (this must be up to a period of years to
» be true). Hence this initial non reaction of future MPB follicles to
» androgens. The above verbiage is related to this»
» Big problem with this guesswork!
»
» Every new hair cycle, the new follicle cells develope from bulge stem
» cells. Stem cells by definition are no “different” from each other, so
» where does this alledged “difference” in follicle makeup come from? my first guess is simply too much androgenic stimulation from too many well-working androgen receptors as evidenced by men having a specific variant of the androgen-receptor gene and the accumulative cag-repeat mutations which make it worse as he ages»

» This also proves Bryans claim wrong, because if follicles need time to
» respond to androgens as he says, we would have normal growth from each
» “new” anagen follicle for a period, before androgens could then “directly”
» cause MPB. We all know this doesn’t happen! Like I said above, some men with MPB start to see it as early as 15 years of age, and alot more do at 20, but several men go through puberty as early as 12 and most do at 13…but hardly anybody is losing hair at 12-14 that I know of. »
» So how do you figure these facts into the direct theory? Fluridil, and the three regrowth photos they have on their site, did alot for me. Fluridil also has a women’s hirsutism study behind it (with a picture if you google it and look) that show it reducing a woman’s moustache to nothing—so we know it works and blocks the androgen receptor. The men (and women) in fluridil testing had no systemic side effects at all, no hormonal changes, as the fluridil degrades in water (and this is the biggest question people have about it----it would be more effective if it was like RU58841 and didn’t degrade so easily, as it probably doesn’t completely coat the dermal papilla’s androgen receptors as well as it should, leaving some ‘open for busines’). The fluridil in no way should get deeper than a hair follicle to affect anything else, yet a couple of the guys had pretty good regrowth and one even had easily evident frontal regrowth. That should have shown you a great deal about your theory being incorrect and wrong.
The direct theory’s greatest support also comes from the fact that baldness is studied in earnest now with alot of money from scientist with microscopic tools who can look all around tissue and see exactly what is happening with staining, etc. None of them is claiming “hey, Im noticing alot of stagnant fluid and conditions of edema”. Not one.
The weak growing body hair transplants, where wavy, weak body hair of men looks exactly the same on the scalp as it does on the body, retaining its growth characteristics when moved, also supports the direct theory of baldness. In fact, alot of the time, it fails to even grow longer in length despite the much better blood supply on the head.
The experiment with RU58841 that moved balding hair to mice that saw only 2 percent of the untreated hair have a second anagen phase vs. 28 percent of the hair treated with RU58841 (they didn’t use nearly enough, something like .01%), shown me that topical RU on a MOUSE’S BACK (no edema there) seen these follicles regrow. Tissue scaffolds were formed, and transplantation was competely performed (or none of them would have regrown), so why didn’t the untreated hairs have second growth phases?
There was more evidence, but Ive more-or-less forgotten about it, because evidence is so overwhelming that the accepted theory is the right one. Have you seen the topical ketoconazole cream’s regrowth pictures? Pretty eye opening, as dutasteride wouldn’t do that much, yet the cream isn’t absorbed through the dermis to affect deeper tissues.

Aside from all of the above…Im interested in real progress in making baldness history. Ralf Paus thinks that anagen-stimulators and catage-suppressors can be used with anti-androgens to treat baldness, and that there is enough stem cells in even long-bald scalp for this to work. I say that you’d better hope like hell Follica or ACELL can make hair up on a bald head, because ICX and Aderans have pretty much failed in the past 6 years of research to produce anything consistent up there. We can keep hair on a man’s head with what we have now. I would venture that finasteride plus RU58841 together would keep a man from even having any signifigant recession for a lifetime if he started using them before he started receeding as the adnrogenic stimulis would just never get high enough. Thats why Im pulling so hard for Follica and ACELL. IF they can simply make new hair on bald scalp, most men could probably keep it with finas and one more receptor-blocking anti-androgen together, be it fluridil, lavender, RU58841, beta sitosterol (if it really works), AJSC9, or whatever receptor -degading topical or blocking topical that comes down the pike. Baldness would then be beaten in a de facto sense while science could keep going after the particular genetic reasons (the androgen-inductible genes that give the papilla the instructions it has post-androgen uptake to release the wrong signals to the rest of the follicle, and why we have cag mutations on that particular variant of the androgen receptor and what we could do about it, even neo-natally do about it so you’d never have to worry about it) later.

53

» We can keep hair on a man’s head with what we have now. I would
» venture that finasteride plus RU58841 together would . . . If they
» can simply make new hair on bald scalp, most men could probably keep it
» with . . . whatever receptor -degading topical or blocking topical that
» comes down the pike. Baldness would then be beaten in a de facto sense.

Sorry to snipe into the conversation raising a side issue, but thinking like this really bothers me.

The current systemic dht inhibitors DO NOT work for enough of us. There are too many of us limiting their Finasteride dosage because of sides, and too many more that are refraining from using the stuff entirely because of it.

I personally don’t even get sides from Fin too badly, and I do see real hair gains. But if Folica works, I’m through with oral Fin. I think I would rather abrade & soak my head again every 5 friggin’ years for the rest of my life if I have to. And I’m probably not alone on that.

This long-term systemic DHT inhibition is not safe. It’s a compromise that’s unfortunate but functional when you’re an older guy on the downside of life’s natural androgen levels and dealing with Prostate cancer. It isn’t right for young healthy guys in their 20s with cosmetic gripes to be on dht-suppression therapy for decades to come.

I think most of us know this on a gut level whether we’re willing to admit it to ourselves or not.

54

» So if it was important that the “radiator” be the MPB area, both sexes
» would have no hair in the MPB area from birth. The “plumbings” the same in
» both sexes, so obviously the “position” of the radiator is not important
» and nothing to do with MPB in humans.

But I’m NOT saying it’s important that the “radiator” be in the MPB area. And that’s probably WHY both human sexes don’t all have missing hair. I’m just saying that it’s helpful in that regard for us to be missing hair on our heads.

» Bryan wrote:
»
» “And that “other story” has been soundly refuted by the Nordstrom study,
» and numerous other considerations. Time to move on, Stephen. Find something
» more productive to do in your spare time.”
»
» You have yet to produce any genuine “science” that refutes my theory
» Bryan. Just trying to claim you have over and over does not make it so!

I just told you in plain English that the Nordstrom study does that, among other observations. The Nordstrom study showed that transplanted balding hair follicles continue to go bald at the same rate, even when transplanted to other another completely different area of the body. Despite your very best efforts, you have never been able to refute that simple and elegant experiment.

» Bryan claims that MPB follicles have to be exposed to androgens for a
» period of time before they respond (this must be up to a period of years
» to be true). Hence this initial non reaction of future MPB follicles
» to androgens.

Actually, I’ve made clear in the past that that’s really just speculation on my part. Nobody really knows for sure what causes scalp hair follciles to gradually become sensitive to androgens ove a period of time. Hopefully we’ll have the answer to that puzzle some day.

» Every new hair cycle, the new follicle cells develope from bulge stem
» cells. Stem cells by definition are no “different” from each other, so
» where does this alledged “difference” in follicle makeup come from?
»
» This also proves Bryans claim wrong, because if follicles need time to
» respond to androgens as he says, we would have normal growth from each
» “new” anagen follicle for a period, before androgens could then “directly”
» cause MPB. We all know this doesn’t happen!

Huh? How do we know that doesn’t happen?? :slight_smile:

.

55

» »» » Every new hair cycle, the new follicle cells develope from bulge stem
» » cells. Stem cells by definition are no “different” from each other, so
» » where does this alledged “difference” in follicle makeup come from?
» »
» » This also proves Bryans claim wrong, because if follicles need time to
» » respond to androgens as he says, we would have normal growth from each
» » “new” anagen follicle for a period, before androgens could then
» “directly”
» » cause MPB. We all know this doesn’t happen!
»
» Huh? How do we know that doesn’t happen?? :slight_smile:

The mutations in the androgen receptor would tend to get worse with age over a man’s life…making each new hair cycle potentially “the” cycle in which androgenic uptake got too high. That is a real possibility»
» .

56

» The mutations in the androgen receptor would tend to get
» worse with age over a man’s life…making each new hair cycle
» potentially “the” cycle in which androgenic uptake got too high. That is a
» real possibility»

I really doubt that further mutations in the androgen receptor have anything at all to do with the sensitization of hair follicles to androgens during/after puberty.

Don’t ask me to specify what it is that DOES cause it, all I’m pretty sure of is what DOESN’T cause it! :stuck_out_tongue:

.

57

» » The mutations in the androgen receptor would tend to get
» » worse with age over a man’s life…making each new hair
» cycle
» » potentially “the” cycle in which androgenic uptake got too high. That is
» a
» » real possibility»
»
» I really doubt that further mutations in the androgen receptor have
» anything at all to do with the sensitization of hair follicles to androgens
» during/after puberty.
»
» Don’t ask me to specify what it is that DOES cause it, all I’m pretty sure
» of is what DOESN’T cause it! :stuck_out_tongue:

What do you think causes sebaceous gland hypertrophy in MPB sujbects?

Do you think there is some “change” in the seabacous glands that makes them mysteriously different and they start issuing diffrent genetic instructions via the sebocytes at some age? Do you think we will find the sebaceous gland-associated genes are different in some way (I dont)?

We know that nizoral usage shrinks sebaceous glands by about 20% (and ketoconazole cream probably shrinks them more than that, and it would be interesting to see just how far RU58841 would shrink them).

I think there is no difference in the sebaceous glands, except that they just get a hell of a lot more androgenic stimulation via the mutated expression of the androgen receptors. I think we have more andorgen recpeptors and better working androgen receptors on parts of our head where the skin grew up over the top of the scalp in fetal development as the ectodysplasin genes went along with the androgen-receptor genes and encoded the intensitiy of androgen-receptor expression in that particular area of skin…

A question, ever notice its the SMALLER PRIMATES WHO BALD THE MOST? Macaques, bonobooos, orangutans, chimps bald more than great big gorillas? Maybe baldness is a side-effect of the males of those groups needing as much androgenic stimulation as they could get to just make it over the millenia, and their androgen receptors being hypersenisitive was a way for them to stay aggressive and energetic enough to make up for their smaller size? It sure as hell seems like smaller, thinner, “scientist-types” go bald a little more than big-burly men do to me for whatever reason…just an observation.

Bryan,
You seem to want to find a “response” genetic difference, but I keep going back to that experiment that added a lot of male hormone to occipital hair and seen it respond just like MPB-hair. My occipital hair IS as good as Jose Canseco’s. I think if you could artificially seed his hair, or somehow potentiate his androgen receptors (sage will supposedly somewhat potentiate the androgen receptor, as well as supress tgf-beta and inhibit collagen formation but thats a different subject), he would start to go MPB. Canseco took steroids for 20 or so years, but still has his hairline intact. I doubt his sebaceous glands are making his hair oily either because his hair never looked greasy to me. But I bet if you could give him my scalp’s androgen-receptor expression on his own scalp, his sebacous glands would indeed enlarge
» and his hair follicles would indeed go bald.

That hairsite posted that info about the alpha-five reductase-related genes being no different in men with MPB and without it, and the fact that I’d be shocked if our sebaceous gland associated-genes are different, and the fact that occipital hair from non-MPB areas will react just like hair from MPB-areas if given enough testosterone, gets me back to the androgen receptor gene----which has been shown in a large-German study to be associated very strongly with baldness.

Repeat mutations on genes get worse with age, I do know that. As they get worse, wouldn’t it be logical for them to invite any “out-of-the-box” responses later and not sooner, just like MPB gets worse with age and more men experience it with age? It makes sense to me. Attepmting to make head hair “like” androgens is something that nobody’s hair on earth, no matter how good it is, really does. Experiments show head hair to be indifferent to male hormone, so attempting to make it “like” male hormone is fundamentally changing something about humanity that heretofore nobody exhibited. Head hair grows in follicular units that are larger than body hair units also. Body hair at most very rarerly grows in a three-hair unit, sometimes in two-hair units, and usually in one hair units. There are five and six-hair follicular units in donor areas on men, and ALOT of two-and-three-hair follicular units on human scalps. Beard hair, the biggest individually on the body, almost always grows one hair at a time------and is coarse and thick and usually wavy. Body hair is often curled and/or wavy, while head hair is straight. So there are some extremely fundamental differences in this hair. I wonder if you could find the androgen-inductible genes post-androgenic uptake and lessen one or two of them and over-express other ones and make head hair like male hormone like body and beard hair does, but you could wind up with head hair that looked lousy like body hair would up there, growing weakly and wavy with smaller hair shafts—but not miniaturizing. HT-docs that move body hair will tell you the body hair might grow longer (about twice as long), but it does not change its characteristics on the scalp at all----it looks just the same as it did on your body.
» .

58

» What do you think causes sebaceous gland hypertrophy in MPB sujbects?
»
» Do you think there is some “change” in the seabacous glands that makes
» them mysteriously different and they start issuing diffrent genetic
» instructions via the sebocytes at some age? Do you think we will find the
» sebaceous gland-associated genes are different in some way (I dont)?
»
» I think there is no difference in the sebaceous glands, except that they
» just get a hell of a lot more androgenic stimulation via the mutated
» expression of the androgen receptors. I think we have more andorgen
» recpeptors and better working androgen receptors on parts of our head where
» the skin grew up over the top of the scalp in fetal development as the
» ectodysplasin genes went along with the androgen-receptor genes and encoded
» the intensitiy of androgen-receptor expression in that particular area of
» skin…

Those are all excellent questions above, and I don’t pretend to know the correct answers. It seems easy enough just to go ahead and assume that sebaceous gland hypertrophy in MPB subjects is a result of greater androgenic stimulation (by way of somewhat higher average androgen levels, AND those pesky overactive androgen receptor polymorphisms which are so closely associated with MPB), but I’m not entirely convinced of that. How does one explain the study that Kligman did several years ago which found that giving normal men extra amounts of androgens orally (as much as 300 mg/day of methyl testosterone, in some cases) had no effect at all on their sebum secretion rates? If all it takes to produce sebaceous gland hypertrophy is greater androgenic stimulation, then why didn’t it happen in Kligman’s test subjects? :wink:

Kligman’s own tentative hypothesis to explain those null results was that even in normal men (men with normal levels of androgens), their sebaceous glands are ALREADY “maxed-out” in response to androgens, so giving them even more produces no extra effect. However, I have a problem of my own with that tentative explanation. Before I state it here, I’d like to hear your response to what I’ve said up to this point.

» Bryan,
» You seem to want to find a “response” genetic difference, but I keep going
» back to that experiment that added a lot of male hormone to occipital hair
» and seen it respond just like MPB-hair.
»
» That hairsite posted that info about the alpha-five reductase-related
» genes being no different in men with MPB and without it, and the fact that
» I’d be shocked if our sebaceous gland associated-genes are different, and
» the fact that occipital hair from non-MPB areas will react just like hair
» from MPB-areas if given enough testosterone, gets me back to the androgen
» receptor gene----which has been shown in a large-German study to be
» associated very strongly with baldness.

Sure, but I’m not nearly as interested in the fact that different scalp hair follicles require differing AMOUNTS of androgens to be negatively affected. I’m far more interested in what causes the different QUALITATIVE responses to androgens, rather than different QUANTITATIVE responses. In other words, I want to know why beard hair follicles thrive and grow strong on androgens, while scalp hair follcles are suppressed by them. I’m not nearly as interested in why occipital follicles require a much greater level of androgens than frontal follicles, to be negatively affected.

» Repeat mutations on genes get worse with age, I do know that.

Can you give me a reference or citation for that?

» As they get
» worse, wouldn’t it be logical for them to invite any “out-of-the-box”
» responses later and not sooner, just like MPB gets worse with age and
» more men experience it with age? It makes sense to me.

Sure, if that really happens (I’d like to see that reference). But even if that weren’t true, I would attribute it to the cumulative damage to hair follicles from years of exposure to androgens.

» Attepmting to make head
» hair “like” androgens is something that nobody’s hair on earth,
» no matter how good it is, really does. […]
» So there are some extremely
» fundamental differences in this hair.

Yes, and I want to know what CAUSES those differences! :slight_smile:

.

59

» »
» Those are all excellent questions above, and I don’t pretend to know the
» correct answers. It seems easy enough just to go ahead and assume
» that sebaceous gland hypertrophy in MPB subjects is a result of greater
» androgenic stimulation (by way of somewhat higher average androgen levels,
» AND those pesky overactive androgen receptor polymorphisms which are so
» closely associated with MPB), but I’m not entirely convinced of that. How
» does one explain the study that Kligman did several years ago which found
» that giving normal men extra amounts of androgens orally (as much as 300
» mg/day of methyl testosterone, in some cases) had no effect at all on their
» sebum secretion rates? If all it takes to produce sebaceous gland
» hypertrophy is greater androgenic stimulation, then why didn’t it happen in
» Kligman’s test subjects? :wink:
I did not know about that Kligman study, and I heartily admit that throws a monkey wrench in what I thought. Hmmm…we know that soy isoflavones topically applied reduced sebum secretion by 65% in one experiment http://www.wipo.int/pctdb/en/wads.jsp?IA=US2003005494&LANGUAGE=EN&ID=090063618014838a&VOL=28&DOC=008576&WO=03/072079&WEEK=36/2003&TYPE=A1&DOC_TYPE=PAMPH&PAGE=1and green tea extract cut it from about 1.20 down to .71, which is almost in half…so cutting androgenic uptake will decrease sebum secretions, so its a suprise that upping androgens wouldn’t up them. As you say, it would appear that the glands are working at full capacity.
»
» Kligman’s own tentative hypothesis to explain those null results was that
» even in normal men (men with normal levels of androgens), their sebaceous
» glands are ALREADY “maxed-out” in response to androgens, so giving them
» even more produces no extra effect. However, I have a problem of my own
» with that tentative explanation. Before I state it here, I’d like to hear
» your response to what I’ve said up to this point. Let me venture a guess, perhaps their alpha five reductase enzymes (type one) were working at full capacity and couldn’t convert anymore T to DHT, or perhaps the androgen receptors they have are already “full” and can’t accept more androgen? Maybe the little glands can only work so hard? About all out of guesses here. That is a “styming” fact. :confused: »

» »» Sure, but I’m not nearly as interested in the fact that different scalp
» hair follicles require differing AMOUNTS of androgens to be negatively
» affected. I’m far more interested in what causes the different QUALITATIVE
» responses to androgens, rather than different QUANTITATIVE responses. In
» other words, I want to know why beard hair follicles thrive and grow strong
» on androgens, while scalp hair follcles are suppressed by them. I’m not
» nearly as interested in why occipital follicles require a much greater
» level of androgens than frontal follicles, to be negatively
» affected. I thought certain androgen inductible genes were activated after androgenic uptake at the receptor site (the step before the alphabet soup growth factors), perhaps these are different in people with certain types of receptor mutations?
»
» » Repeat mutations on genes get worse with age, I do know that.
»
» Can you give me a reference or citation for that? I’d always heard that, Ive never bothered to look it up. I’ll try and spend a little time with google. I thought that was why diseases tended to get worse with age…
»
» »» Sure, if that really happens (I’d like to see that reference). But even
» if that weren’t true, I would attribute it to the cumulative damage
» to hair follicles from years of exposure to androgens. This is where I have had observances that make me think otherwise. Ive posted ad nauseaum in the past pictures of women who took testosterone to be like men, and they went bald in some cases rather quickly----as in less than two years. I can dig some of those photos up online if you’d like but if you web search “Oprah when your identical twin has a sex change” or a particular porn star who was once a very pretty women, but is now a bald-headed, mustached, kinda built up man…cant think of her name, but its on hlt, there was another porn star named “van diesel” who took roids and has a big, heavy beard, and is bald, with a hairy body now. I once found an entire page of pictures of female-to-male transexuals. They had beards and some were bald. There was even a youtube video of one of them talking about taking finasteride and rogaine, and how she gave up on it. She was completely bald and looked just like a man in the face. Testosterone ages the living daylights out of these womens faces. It doesn’t take long if they have baldness genetically Oprah.com …thats the Oprah link.

The myspace site of “Buck Angel” who used to be a pretty woman with pretty blonde hair. Ive posted her old “female” pic before and its hard to believe. She is still a female with female genitalia.

Van Diesel, the pornstar…http://www.gamelink.com/display_product.jhtml?id=282568 Yes, that is a woman…I know, yuck. Hairy chest and all. Always has something on the head…because she is bald.

The balding of these women didn’t take long…thats why the “cumulative” idea of ROS doing in hair follicles over many years seems unlikely to me personally. What about the men who start losing it at 16 and are bald by 23? Thats why I always had a problem with that.
»
» » Attepmting to make head
» » hair “like” androgens is something that nobody’s hair on earth,
» » no matter how good it is, really does. […]
» » So there are some extremely
» » fundamental differences in this hair.
»
» Yes, and I want to know what CAUSES those differences! :slight_smile: Im guessing the genes activated by the receptor might very well be different in some men with mutated receptors, but if not, we are back to the “your hair is just different” approach–which would be dissapointing news.

BTW–did you see the getfitinib picture in the HM forum. Some guy took it and regrew quite alot of hair in the middle of a bald scalp. He had been bald for a long time. The new hair was dark, but kinda looks like thick body hair to me. This is an older man by the looks of it. Getfitinib is the preferred egf-receptor blocker in the follica patent. The deal is (I dont know if you follow HM or not) is that they wound the scalp through dermabrasion and block epidermal growth factor so the epilithial cells are forced to build hair follicles instead of grow new skin. It works on human skin grafted to a scid mouse, and it works on various animals. It even worked on genetically hairless mice. Im pretty excited about this because just perhaps, if science can block certain genes during this hairs development (hair germs were detected in human skin on a scid mouse just seven days post abrasion), just maybe the hair “made” might not be MPB in the future if it will work in vivo.
»
» .

60

» » »

»
»
» BTW–did you see the getfitinib picture in the HM forum. Some guy took it
» and regrew quite alot of hair in the middle of a bald scalp. He had been
» bald for a long time. The new hair was dark, but kinda looks like thick
» body hair to me.

Man, if Folica’s real method turns out to only be able to regenerate body hair on the scalp, we’re gonna be some pretty effing unhappy campers.

Personally I think the hair (on the Gentifib cancer patient) looked more like it was just very weak scalp hair. The density, the straightness, etc.

I also just think the scalp skin is only gonna have the right genetic instructions for one type of hair - scalp or body type, but not both. (If it was remotely possible to grow body hair on the scalp then I think we would have stumbled onto at least a few examples of it a long time ago.)

I’ve also wondered what existing HT grafts would do to the Folica method.

If the Folica method is creating all-new follicles, then that genetic info is coming from the raw skin. But what happens when the raw skin is giving conflicting signals? A modern HT graft is basically a chunk of androgen-resistant skin tissue that has been lodged into an otherwise androgen-sensitive area of the scalp. What kind of androgen resistance does an all-new Folica graft develop at that site? Something in the middle?