Pillows, Pillows, Pillows..??..

[michael barry]

Bryan,

You mention that you favor Whiting's "genetic clock" theory.................


Im kind of developing a different idea in my mind based on some of studies Doctor posted and some Ive read in the past.


Fact: We know alpha five reductase gets more active as men age. I dont know if this means more alpha five reductase enzymes are made, they get better at what they do, they are more chemically stable, etc. However, what I do know is that men's body hair gets hairier and hairier, leading many men to have really "peak" body hair in their forties and fifties, when many men with "good" hair, start to see bald spots and recession.


Fact: We see in other androgen related disorders (like the studies Ive posted), that androgen receptor expression is heightened and we also have the repeat mutations in androgen receptors that Doctor has generously detailed for us.


Fact: Head hair needs no male hormone and grows well without any of it.




My idea: Male hormone isn't necessary for head hair, and your head hair can deal with some androgenic transcription up to a point, but as alpha five increases with age and androgen receptor expression might also increase with age "up there", there gets to be more than what head hair "can handle" and it starts growing more weakly and apoptosis begins, the collagen deposition around the hairs begin, immuno events might occur, etc. IMPORTANT: Im not saying some men's hair isn't more "resiliant" against androgens than others.........

BUT, what I am saying is that there may be no "genetic clock" within cells "somewhere" in the philosebaceous unit that tell the dermal papilla cells "at age 39, you will begin to have a bad response (or cough, if you will) when you uptake DHT through a receptor site).



Lemme, Bryan, base this on a couple of observations. Ive shown people with 4 pics and a study of 13 women, that women basically have male pattern baldness just like men do, but dont have the hormones to kick it off. But they go bald just like a man does if you give them testosterone if their family genetics dictate that.


When I look at men who have full heads of hair Bryan................no recession in their mid-thirties and forties...........................Their hair still greys sooner, is more brittle, and has an "aged"-look as opposed to females of the same age. The only men Ive noticed whose hair is practically "the same" as females are young hispanics in their twenties still. They have hair that is so thick and the follicles so large that it could pass for a woman's hair pretty easily. But Ive noticed as they age............even with no recession, many get a little thin in the vertex and the "look" of the hair gets dryer, more brittle, and more grey while the dark women's just doesn't change (until they get post-menaupausal).


I think we are going to find that its the volume of androgen uptake that makes us bald more than anything.......................which is a "mix" of how active your alpha five reductase enyzme in the root sheath is, and how much androgen receptor expression that you have (and possibly this might be effected to a small extent by having more of the other androgens than normal in the scalp area also through low globulin, alot of type 1 DHT also).



Thats my own little guess anyway.
I suppose I could use body hair to relate this in another way. We konw that a "smooth man" (Brad Pitt) can have every bit as much serum DHT and T than a "hairy man" (Steve Carrell----have you ever seen his chest? A forrest), but why does Steve Carrell have chest hair like an ape and Brad Pitt have almost none? My guess is that Steve's androgen receptors on those hairs just perform better and the alpha five reductase enzymes near those chest hairs just are better at making more DHT from available testosterone. We KNOW that most all DHT gets bound by globulin when it gets out into the body right? Its the only thing that really makes sense, as the vellus hairs on Brad Pitt's body surely have the same "male body hair" general genetic make-up as any other guy. Pitt strikes me as a fairly "manly" dude with normal testosterone levels, so why isn't his chest a forrest like Carrell's or well,.............mine?


There you folks have my own little hairloss theory. Feel free to make as much fun of it as you want : )

 

[docj077]

I think that the fact that the growth inhibition is dose AND time related speaks volumes. That means that not only are androgens causing growth inhibition with increasing doses, but it also means that the cells require exposure for a specific length of time in order to upregulate the cellular machinary necessary to transcribe and translate the genes necessary for growth inhibition to occur.

But does it seem reasonable that it could take DECADES for that to occur? I personally was in my 40's before I noticed my thinning spot.

I tend to favor the "genetic clock" theory mentioned by Whiting: there's a relatively sudden period in which scalp follicles start to become more sensitive to androgens. I wish we knew what precipitates it.

Very reasonable and not surprising whatsoever. The "genetic clock" theory is very interesting, but I'd be far more in favor of examining the external environment that surround the hair follicle and the follicle itself sans the keratinocytes. The delay could very possibly be due to the function of fibroblasts and not necessarily due to the need to reach a particular androgen response threshold. It could just be that individuals predisposed to baldness reach that threshold right after adrenarche, but the general progression is determined by the genetic predisposition to wound healing (ie TGF-beta response) in those individuals.

 

[michael barry]

Doctor,

what do you think of this:


Balding guy (for example) has 100 androgen receptors per hair
Non-balding guy.............. has 50 androgen receptors per hair


Balding men, as we know, were found to have 3 times as much DHT in balding scalp than non-bald scalp.


so.............
Balding guy has 90 receptor sites filled with DHT molecules
Non-balding guy has 30 receptor sites filled with DHT molecules





See what Im getting at man?
Im not saying that some men have hair that is more resistant to testosterone or its metabolites, but Im saying that men who have baldness just proabably are getting a hell of a lot more androgenic uptake in the follicles. If Brad Pitt was getting the androgenic uptake as Bruce Willis, he might not be bald yet, but I think he'd be thinning a great deal. Thats my guess.

 

[powersam]

michael barry and armando, can you please use the quote function? in some of those longer posts its hard to follow who said what.

That thing never works for me.................LOL.

I agree with Sam that it's very difficult to read and understand when you don't use the "quote" function. Let's find out what the problem is: what actually happens when you click the "Quote" button?

he needs to unclick the disable html option. it appears in your profile and underneath this box you type your post into.

 

[michael barry]

nnnbbbb

 

[docj077]

Doctor,

what do you think of this:


Balding guy (for example) has 100 androgen receptors per hair
Non-balding guy.............. has 50 androgen receptors per hair


Balding men, as we know, were found to have 3 times as much DHT in balding scalp than non-bald scalp.


so.............
Balding guy has 90 receptor sites filled with DHT molecules
Non-balding guy has 30 receptor sites filled with DHT molecules





See what Im getting at man?
Im not saying that some men have hair that is more resistant to testosterone or its metabolites, but Im saying that men who have baldness just proabably are getting a hell of a lot more androgenic uptake in the follicles. If Brad Pitt was getting the androgenic uptake as Bruce Willis, he might not be bald yet, but I think he'd be thinning a great deal. Thats my guess.

I agree with you 100%. An increase in receptor concentration combined with an increase in androgen production locally will lead to a greater physiological response; whether it be stimulatory or inhibitory. In the case of male pattern baldness, it appears to be inhibitory. More androgen/androgen receptor complexes means more DNA binding, and thus, more DNA transcription and translation. What you're talking about is well documented and any medical biochemistry or physiology textbook will discuss it.

 

[powersam]

nnnbbbb

WOOOOOOOT

 

[Bryan]

he needs to unclick the disable html option. it appears in your profile and underneath this box you type your post into.

Why would it stop the "Quote" button from working properly, if the "Disable HTML" option is clicked?

By the way, even my OWN "Disable HTML" option is clicked, and yet it's not stopping me from using the "Quote" function.

 

[Bryan]

My idea: Male hormone isn't necessary for head hair, and your head hair can deal with some androgenic transcription up to a point, but as alpha five increases with age and androgen receptor expression might also increase with age "up there", there gets to be more than what head hair "can handle" and it starts growing more weakly and apoptosis begins, the collagen deposition around the hairs begin, immuno events might occur, etc. IMPORTANT: Im not saying some men's hair isn't more "resiliant" against androgens than others......

I feel like I've slipped into some Bizarro parallel universe, because once again I'm going to have to take up for what Stephen Foote has been saying in this thread!

Stephen has been saying (and I fully agree with him on this) that experiments clearly show that scalp hair follicles show a different response to androgens, depending on variables and circumstances that are still unknown to us (well, Stephen thinks he knows what causes it, but that's where he and I part company). It's not just a different LEVEL of androgenic stimulation (like greater or lesser numbers of androgen receptors, or greater or lesser levels of testosterone and/or DHT). Stephen cited the Japanese study in which those simple and obvious issues were rigorously controlled and accounted for: they used a fixed level of the powerful synthetic androgen R1881 (it isn't metabolized into anything else, so the level of 5a-reductase was no longer even an issue), and they transfected androgen receptors equally into all follicles cells and even PROVED that they were functioning similarly in all the samples, regardless of whether the cells came from balding or non-balding sites. And under those rigorously controlled conditions (controlled for levels of androgen AND androgen receptors), there was _still_ a clear diffference in TGF beta-1 production between the balding cells and the non-balding cells.

That's what Stephen was trying to get across to you guys, without much success! There simply is no explanation (yet) for that phenomenon. We don't know (yet) what causes pre-balding hair follicles to eventually become sensitive ENOUGH to androgens that they start to go bald. It's something OTHER than just levels of androgens and androgen receptors. It's something that so far remains mysterious! :freaked:

 

[michael barry]

Bryan,

What Im getting at is that hairs BECOME male pattern baldness hairs because of a higher degree of androgenic stimulation in the first place. Brad Pitts hair no doubt uptakes male hormone, but the levels of such have never been high enough to make his hair respond negatively to it yet.

I bet if his hair uptook as much DHT as a really bald guys did over a good year or so, it would start to become sensitive to it. I think its the consistent high androgen stimulis that forces a change in hair follicles so that they exhibit minaiturization.


After they "become" male pattern baldness hairs, THEN they weaken growth with androgen stimulis. What you submitted was something that tested known miniaturizaing hairs against non-miniaturizing hars.

 

[docj077]

I feel like I've slipped into some Bizarro parallel universe, because once again I'm going to have to take up for what Stephen Foote has been saying in this thread!

Stephen has been saying (and I fully agree with him on this) that experiments clearly show that scalp hair follicles show a different response to androgens, depending on variables and circumstances that are still unknown to us (well, Stephen thinks he knows what causes it, but that's where he and I part company). It's not just a different LEVEL of androgenic stimulation (like greater or lesser numbers of androgen receptors, or greater or lesser levels of testosterone and/or DHT). Stephen cited the Japanese study in which those simple and obvious issues were rigorously controlled and accounted for: they used a fixed level of the powerful synthetic androgen R1881 (it isn't metabolized into anything else, so the level of 5a-reductase was no longer even an issue), and they transfected androgen receptors equally into all follicles cells and even PROVED that they were functioning similarly in all the samples, regardless of whether the cells came from balding or non-balding sites. And under those rigorously controlled conditions (controlled for levels of androgen AND androgen receptors), there was _still_ a clear diffference in TGF beta-1 production between the balding cells and the non-balding cells.

Bryan, was the study controlled for all cell types? I have not read this study...I don't think. I'm interested to know if the study controlled for androgen receptor concentration across all cell types including all cells within the follicle that could potentially have androgen receptors such as dermal fibroblasts. Afterall, those are the cells that are responsible for the keratinocyte inhibition and perifollicular fibrosis. The entire follicular unit must be intact in order for the study to work and any difference in fibroblast count, gene methylation/activation, or response will be quite noticeable in terms of TGF-beta concentrations.

 

[Bryan]

Bryan,

What Im getting at is that hairs BECOME male pattern baldness hairs because of a higher degree of androgenic stimulation in the first place...After they "become" male pattern baldness hairs, THEN they weaken growth with androgen stimulis. What you submitted was something that tested known miniaturizaing hairs against non-miniaturizing hars.

Sure, that's one of the possibilities I've pointed out to Stephen for years, but he's always hooted at the idea, saying there's no known example or precedent for such an alleged phenomenon anywhere in biology. How would YOU answer him on that?

 

[michael barry]

Bryan,

I would say that we know women usually have approximately one tenth the testostgerone that men do, therefore probably around 10 percent the amount of DHT transcription also.

IF that is so, what if we could tweak the testosterone up to 20% of a man's levels, and see what happens. If nothing happens, lets try 30%. At some point, if you did this with a group of 20 women, some of the women would start to see some frontal recession if the experiment took place over a year or so between adjusting the testosterone increases. Over time, probably before you got up to 50-60% of normal male testsoterone levels, I'd imagine 2-3 females would be losing hair at year three, four, or five. Im assuming we'd be using caucasoid females.


Or I suppose the experiment could use males castrated at puberty (but there probably aren't many of those around).


IF just small amounts of T were necessary for miniaturizaion, women would no doubt be going bald......................especially women in things like sprinting or other hard exertion sports as Im pretty sure a female weightlifter would have higher than average amounts of T. I dont think 20% would be enough to do it...........................but I bet as we got in the thirties and forties, we really might see something. That would be my guess.

 

[Bryan]

Bryan, was the study controlled for all cell types? I have not read this study...I don't think.

They used dermal papilla cells and keratinocytes in one of those "co-culture" experiments, like Uno first did in his stumptailed macaque study. Here's the link:

http://www.fasebj.org/cgi/content/full/16/14/1967

I'm interested to know if the study controlled for androgen receptor concentration across all cell types including all cells within the follicle that could potentially have androgen receptors such as dermal fibroblasts. Afterall, those are the cells that are responsible for the keratinocyte inhibition and perifollicular fibrosis. The entire follicular unit must be intact in order for the study to work and any difference in fibroblast count, gene methylation/activation, or response will be quite noticeable in terms of TGF-beta concentrations.

It's the interaction between dermal papilla cells and keratinocytes which is currently considered to be the critical factor. There are now at least two or three studies dealing with the co-culture of those cell types, and they're presenting a consistent picture.

 

[Bryan]

Bryan,

I would say that we know women usually have approximately one tenth the testostgerone that men do, therefore probably around 10 percent the amount of DHT transcription also.

IF that is so, what if we could tweak the testosterone up to 20% of a man's levels, and see what happens. If nothing happens, lets try 30%. At some point, if you did this with a group of 20 women, some of the women would start to see some frontal recession if the experiment took place over a year or so between adjusting the testosterone increases. Over time, probably before you got up to 50-60% of normal male testsoterone levels, I'd imagine 2-3 females would be losing hair at year three, four, or five. Im assuming we'd be using caucasoid females.

Sure, but that's not what we're talking about. The scenario you describe above just has to do with the more mundane issue of HOW MUCH androgen is required for people to start balding, who are already in a "balding mode".

What Stephen and I are talking about is something much much more specific: what CAUSES a hair follicle from a young person (or from essentialy any pre-balding person) which is unaffected by androgens (even by large quantities of androgens) to BECOME sensitive to them at a later time? That's the fundamental puzzle here. It's the one that Stephen is interested in, because at present there is no definitive answer for it, just speculation. He likes that, for obvious reasons! :wink:

 

[michael barry]

Bryan,

My conjecture was that pre-balding hairs in young men have not faced the higher levels of androgens that they face when they are balding later in their thirties.

Im postulating that a guy who is going to go bald but isn't balding at 20 has less alpha five reductase activity at 20, and his androgen receptors may not be as numerous, chemically stable, or as well-functioning.


Im postulating that every person has a "limit" to how many androgens their hairs can take, and that is almost certainly different upon each and every individual, before their hairs start to react negatively to it downstream of dermal papilla uptake of androgens. Im thinking there is a toxic threshold at play here based on the fact that occipital hair follicles were made to react negatively to high androgen stimulis in that old experiment (or cells rather for Stephen). It shows that even they, with less receptors, have a limit to how much androgen they can take.

Who knows, maybe there is even a limit to how much body hairs can take too (and I dont mean physcially drowning them).


Id like to pluck a hair from Tom Cruise..........................transfect it with as many androgen receptors as Bruce Willis has in his hairs..............and subject it to as much testosterone and DHT as Willis hair deals with in his fifities. If they could somehow culture the hair for one good month...........I wonder if it would start to slow cell division in the keratinocytes. This is simply theoretical speculation though.


There very well may be a difference between head hairs based on how your skin grows over your head in fetal development that cellularily seals their fate right then. As you have said before Bryan, they are working on it, and I guess they will know someday. I hope Im still around when they figure it out though.

 

[docj077]

Bryan, was the study controlled for all cell types? I have not read this study...I don't think.

They used dermal papilla cells and keratinocytes in one of those "co-culture" experiments, like Uno first did in his stumptailed macaque study. Here's the link:

http://www.fasebj.org/cgi/content/full/16/14/1967

I'm interested to know if the study controlled for androgen receptor concentration across all cell types including all cells within the follicle that could potentially have androgen receptors such as dermal fibroblasts. Afterall, those are the cells that are responsible for the keratinocyte inhibition and perifollicular fibrosis. The entire follicular unit must be intact in order for the study to work and any difference in fibroblast count, gene methylation/activation, or response will be quite noticeable in terms of TGF-beta concentrations.

It's the interaction between dermal papilla cells and keratinocytes which is currently considered to be the critical factor. There are now at least two or three studies dealing with the co-culture of those cell types, and they're presenting a consistent picture.

I would have a problem with any study that didn't look at dermal fibroblasts as a significant source of follicular inhibition. Yes, the dermal papillae cells are important in the inhibitory response, but the dermal fibroblasts are what maintain that inhibition long term in terms of perifollicular remodeling.

 

[wookster]

If you could pluck five hairs from David Beckhams frontal scalp, and measure the androgen receptors, and the amount of alpha five created........................................I have a hunch that you would find that he has much less receptor expression in his hair and much less alpha five around his hair follicles also. If we could synthetically add androgen receptors to five of his cultivated hairs in an experiment and add as much DHT as a balding guy's balding hair makes..................we might be suprised as Beckham's unreceeded hair's might react negatively to it.

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

Genetic analysis of male pattern baldness and the 5alpha-reductase genes.

Ellis JA, Stebbing M, Harrap SB.

Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia.

[...]

From a population survey of 828 healthy families comprising 3000 individuals, we identified 58 young bald men (aged 18-30 y) and 114 older nonbald men (aged 50-70 y) for a case control comparison. No significant differences were found between cases and controls in allele, genotype, or haplotype frequencies for restriction fragment length polymorphisms of either gene. These findings suggest that the genes encoding the two 5alpha-reductase isoenzymes are not associated with male pattern baldness. Finally, no clear inheritance pattern of male pattern baldness was observed. The relatively strong concordance for baldness between fathers and sons in this study was not consistent with a simple Mendelian autosomal dominant inheritance.

 

[michael barry]

Wook,

That is interesting.


I had read that balding scalp has 3 to 3 and a half times as much alpha five reductase (and probably have posted it somewhere on this thread) and more androgen receptors were detected--Sawaya.

If the two genes that code alpha five reductase are no different.............why then is there more DHT in balding areas of the scalp and a T/DHT ratio so skewed in favor of DHT?

It just doesn't make sense does it?

 

[wookster]

Wook,

That is interesting.


I had read that balding scalp has 3 to 3 and a half times as much alpha five reductase (and probably have posted it somewhere on this thread) and more androgen receptors were detected--Sawaya.

If the two genes that code alpha five reductase are no different.............why then is there more DHT in balding areas of the scalp and a T/DHT ratio so skewed in favor of DHT?

It just doesn't make sense does it?

An interesting case of hypertrichosis, trichomegaly and nipple retraction:

http://dermatology.cdlib.org/122/case_p ... ghaei.html

Caused by DHT?