What type of persons are more vulnerable to hairloss?

[hair today gone tomorrow]

Hair without sebum is brittle, dull, not shimmering and easly broken.

If persons with CAIS have a luxuriant scalp hair, probably they have sebum. It could be interesting make a experiment to demostrate it.

Armando

Armando...thats is your response to MICHAELS post...c'mon man...enough is enough...give it a rest.

 

[Bryan]

Listen carefully and try to understand what I'm telling you: those specific changes aren't androgen dependent, they are due to other factors that influence hair growth.

Your "WHOLE" argument in your original post that i linked, was that the so called androgen "dependant" follicles, were in effect "IMMUNE" from any other external influence, so demonstrating so called "donor dominance"!!!! Why? because of the "no change in growth" they appeared to demonstrate :freaked2: :freaked2:

Now you try a complete U turn, and expect everyone to just go along with you :roll:

Nowhere in that post did I ever state that androgen dependent hair follicles are "immune" from any other external influence.

I'll make yet another attempt to explain it to you, Junior: I'm saying now, like I have ALWAYS said, that hair follicles demonstrate donor dominance in the way that they respond to androgens. However, a more recent experiment does seem to show that hair follicles do indeed seem to have somewhat altered growth rates in response to other factors, too, which can be influenced by their location on the body. That's not a "U turn", dumbbell, it's just an acknowledgement of the scientific evidence.

It's obvious from your childish name-calling and accusations in the last couple of your posts here that I've really hit a nerve in you by dismantling what you THOUGHT was going to be a successful attempt to disprove donor dominance! Better luck next time, Stephen! :wink:

 

[michael barry]

Armando,

Byran has posted the sebum levels of persons with CAIS, and they are about nil. Almost nothing, and less than children's. Im sure he'd be happy to post that.


Nose hair doesn't need sebum. My finger hair (Im a pretty damn hairy human being) is about the size of hairline hair. I have toe hairs on my big toe that are as big as human head hair------------dont think there is any sebum down there either.

Sebum lubricates the skin, aids in waterpoofing from years of very long Christmas past, and probably is photoprotective against the sun. We'd be rather "dry" without it as human beings, and Im of course glad that we have it. The sebaceous glands are located near "holes" in the dermis where the sebum they produce can "ride" hair as it grows out onto the surface of the skin and thus lubricate the skin and be photoprotective, etc. However, they are in the dermis for dermatological and not trichotic reasons.

The phenomena you describe (sebum interrupting the flow of stem cells as it gets backed up inhibiting the papilla's need for stem cell galvanization) simply isn't whats happening in Male Pattern Baldness. Finasteride (or for that matter minoxidil) would not be having the positive effects that they have if it were so. A drug like MK386, which really does inhibit sebum manufacture, would very much help human head hair if that were the case.

Transplants would eventually fall out when moved up front in the scalp also if that were the case, but they obviously dont...................so where does that leave us?


What is a shame about all of this is what a colossal waste of time so many "alternative" theories about human baldness represent. Guys logging onto forums are eager to believe that their own genetics aren't making them bald, and that people didn't bald as much in the past (the Romans were so interested in baldness that one of the emporers wrote a book about it, the Egyptians were the first people to come up with "cures" for it involving hippo shitt and crocodile fat, the greeks noticed eunuchs never went bald if they were castrated before baldness started, even if all the other men in their family did). Baldness has been represented in art all the way back to ancient Sumeria, and Ive seen a vase from Crete dated at 1500 BC that showed a bald-headed, beareded fisherman. His hair was medium length on the sides. Its not shampoo, modern stress, haircuts that cause common baldness. The increase in skin androgens due to insulin-resistance diets probably speed baldness up a bit (as evidenced in Japanese now balding SOONER than what they used to), and certain foodstuffs like green tea and soya might aid against baldness to a degree by anti-androgeic (i.e. natural propecia) methods, but male pattern baldness is genetic.

Im "testing" Stephen's idea formally with an ice pack on my knee while I read the net (Im a net junkie, and spend a good hour a day online), so his idea is getting a look now. In about four more months I'll be able to say "hey the cold is a stimulant" or "hey, the cold didn't do anything".

My belief is that docs are right about male pattern baldness, and that people's head hair can only take so much androgens....................and for some of us it ain't much. The negative response is followed by an immuno attack that inflammes the area (probably due to the overexpression of TGF beta) and baldness and fibrosis ensues. Just like the professionals like Ralf Paus, Kevin McElwee, Stenn, Costarialis, Washenik, Sawaya, Cooley, Orentriech, Limmer et al say. ALot of BRILLIANT people would have to be wrong about baldness for an alternate theory to be correct Armando.

 

[S Foote.]

Listen carefully and try to understand what I'm telling you: those specific changes aren't androgen dependent, they are due to other factors that influence hair growth.

Your "WHOLE" argument in your original post that i linked, was that the so called androgen "dependant" follicles, were in effect "IMMUNE" from any other external influence, so demonstrating so called "donor dominance"!!!! Why? because of the "no change in growth" they appeared to demonstrate :freaked2: :freaked2:

Now you try a complete U turn, and expect everyone to just go along with you :roll:

Nowhere in that post did I ever state that androgen dependent hair follicles are "immune" from any other external influence.

I'll make yet another attempt to explain it to you, Junior: I'm saying now, like I have ALWAYS said, that hair follicles demonstrate donor dominance in the way that they respond to androgens. However, a more recent experiment does seem to show that hair follicles do indeed seem to have somewhat altered growth rates in response to other factors, too, which can be influenced by their location on the body. That's not a "U turn", dumbbell, it's just an acknowledgement of the scientific evidence.

It's obvious from your childish name-calling and accusations in the last couple of your posts here that I've really hit a nerve in you by dismantling what you THOUGHT was going to be a successful attempt to disprove donor dominance! Better luck next time, Stephen! :wink:

So let's recap then?

In the original thread you started about donor dominance, the transplanted balding follicles maintained their original growth rates when transplanted to other area's. You claimed in that thread that this "proved" a "locked in" direct androgen control on the follicles growth rate with no possible outside factors.

But it seems that when "other" follicles you also claim are androgen dependant for their growth rate "DO" change growth when transplanted, "OTHER" factors "THEN" become important! :freaked: :freaked:

You just don't seem to understand how ridiculous that argument is in scientific terms :roll:

I call you out as i see you Bryan. You have no scientific integrety whatsoever in these debates, your intention is only to try to convince people on internet forums that you are some kind of expert :roll:

I am sure there are many other people on these forums that see through you, but they keep quiet because they have seen the verbal abuse you revert too when you are criticised.

The facts speak for themselves Bryan, as do your "variable" opinions. 8)

S Foote.

 

[docj077]

What the hell is all this talk about indirect vs. direct when it comes to hair loss theory? From what I've read, the current scientifically and medically correct theory dictates that androgens promote hair loss in males with either single nucleotide repeat mutations or triplet repeat mutations in their androgen receptors through the actions of TGF-beta. This increase induces apoptosis in nearby keratinocytes and thereby inhibits the pro-proliferative and anti-apoptotic effects that the defective androgen receptor has at the biochemical level. There are numerous other signaling pathways that are also inhibited, which seem to prevent the hair follicle from cycling correctly, but the majority of the growth inhibition comes from the keratinocyte death, the deposition of collagen, and hyperkeratinization of the epidermis.

What is so difficult about this?

There is nothing direct about any theory in hair loss. If it involves more than one step, then it sure isn't direct.

 

[michael barry]

Doctor,

Yes, its amusing isn't it?
Armando persists on insisting that sebum backing up and interfereing with stem cell migration to the dermal papilla is causing all the events in baldness.

Despite the fact that finasteride (no effect on sebum) alone disproves this,
and the fact that hair transplants disprove it also, and the fact that Merks' MK386 which lowers sebum secretions a great deal but only has a slightly positive effect on head hair just eludes the living hell out of Armando who keeps insisting that if we just all grew our hair long, we'd all keep it.


Doctor, have you looked at the new fluridil studies? They look very promising, especially the increased hair diameters in the women's alopecia study.

 

[Armando Jose]

Michael:

Why in our body only in the back of hands and feet where don’t exist hair we have not sebaceous glands?

Mostly of sebaceous gland are associated with hair.

And if you think that male pattern baldness is only genetic, why do you are looking for a solution when genetic medicine is not available today?

Exists any difference in healthy scalp hairs between sexes?
I don’t know any study and I imagine that NATURE (not the squanderer nature) did not make two different systems for the more complex “organâ€￾ in our body.

Maybe some of our friends in this community are right and I am only a snake oil con artist, although it is very dubious.
My option to prevent (better prevention than cure) is totally FREE. Women know it very well. I also have developed a product, a hair tonic and a shampoo, to try to recover the last hair lost but it is not a treatment for life, like the only two approved by FDA.
I am not a good businessman, but I think I am honest with myself because I made a theory in order to explain the observed facts in common baldness, or in order to give credibility at my product. Opps, I don’t remember now, what was first if the product or the theory. But I am not the only in this aspect, some others real scientists could make the same:
Hair Transplant - Donor dominance
Minoxidil - Nutrient and circulatory events
Propecia - Androgens events
Grow your hair - Sebum low problems

Nowadays donor dominance theory and even androgenetic theory are on the spot.

Who is right and who is wrong? The time will pass judgment.

Armando

 

[michael barry]

Ive got alot of hair on the back of my hand, and fingers too.


I think you mean the palms of the hand and the soles of the feet.


What about nosehair? we all have hair in our noses, and there are no sebaceous glands there. Finger hair? Toe hair? EAR HAIR


Maybe you are a true believer. Ive noticed that when folks decide to commit to a theory, nothng will seemingly shake their beleif in that theory. Ive seen a bazillion buzz-cut guys with full heads of hair, but that makes no difference to you-------------as does the success of finas (no effect on sebum), hair transplants, etc.


Your theory is wrong, and it will be as forgotten as tight hats/baldness in a few years.

 

[Bryan]

So let's recap then?

In the original thread you started about donor dominance, the transplanted balding follicles maintained their original growth rates when transplanted to other area's. You claimed in that thread that this "proved" a "locked in" direct androgen control on the follicles growth rate with no possible outside factors.

I have a minor quibble or two with the way you phrased all that (for example, I don't believe I said anything about "no possibility" of outside factors), but yes, that's basically correct.

But it seems that when "other" follicles you also claim are androgen dependant for their growth rate "DO" change growth when transplanted, "OTHER" factors "THEN" become important! :freaked: :freaked:

Yes, that's also pretty much correct, although those "other" follicles aren't "androgen dependent" in the same way as the follicles in the first case; furthermore, I would use the phrase "other factors then become important" with more caution than you do (which should be a hint to you about where I'm coming from with all this! :wink: ).

You just don't seem to understand how ridiculous that argument is in scientific terms :roll:

What exactly do you find "ridiculous" about it? Let's get all this out in the open, so state your objections as clearly and precisely as possible.

I'm really looking forward to this discussion! :wink:

 

[S Foote.]

What the hell is all this talk about indirect vs. direct when it comes to hair loss theory? From what I've read, the current scientifically and medically correct theory dictates that androgens promote hair loss in males with either single nucleotide repeat mutations or triplet repeat mutations in their androgen receptors through the actions of TGF-beta. This increase induces apoptosis in nearby keratinocytes and thereby inhibits the pro-proliferative and anti-apoptotic effects that the defective androgen receptor has at the biochemical level. There are numerous other signaling pathways that are also inhibited, which seem to prevent the hair follicle from cycling correctly, but the majority of the growth inhibition comes from the keratinocyte death, the deposition of collagen, and hyperkeratinization of the epidermis.

What is so difficult about this?

There is nothing direct about any theory in hair loss. If it involves more than one step, then it sure isn't direct.

So while all the reputable scientists admit they know very little about the details of androgen related hair growth/loss, "YOU" do! Why, because you read it somewhere!

I have some questions for you about your statement above, but first i want you to clear something up?

You post here as "Doctor". I have seen some posts where people have refered to you as a Doctor, and i have not seen you deny this.

If you are a qualified Doctor, i would like to know your qualification. Because if you are "NOT" a Doctor, you are misrepresenting yourself on these forums to some vunerable people.

I think the admin of this site should insist you change your handle, if you are not a "genuine" Doctor. So please post your qualifications.

S Foote.

 

[S Foote.]

So let's recap then?

In the original thread you started about donor dominance, the transplanted balding follicles maintained their original growth rates when transplanted to other area's. You claimed in that thread that this "proved" a "locked in" direct androgen control on the follicles growth rate with no possible outside factors.

I have a minor quibble or two with the way you phrased all that (for example, I don't believe I said anything about "no possibility" of outside factors), but yes, that's basically correct.

[quote="S Foote.":d40da]But it seems that when "other" follicles you also claim are androgen dependant for their growth rate "DO" change growth when transplanted, "OTHER" factors "THEN" become important! :freaked: :freaked:

Yes, that's also pretty much correct, although those "other" follicles aren't "androgen dependent" in the same way as the follicles in the first case; furthermore, I would use the phrase "other factors then become important" with more caution than you do (which should be a hint to you about where I'm coming from with all this! :wink: ).

You just don't seem to understand how ridiculous that argument is in scientific terms :roll:

What exactly do you find "ridiculous" about it? Let's get all this out in the open, so state your objections as clearly and precisely as possible.

I'm really looking forward to this discussion! :wink:[/quote:d40da]

Well Bryan, your own words on the subject in the link i posted clearly demonstrate my point here.

Quote (again!)

"All of these oddball theories were soundly refuted with the advent of modern hair transplantation, which proved that hair follicles continue to grow (or go bald, for that matter), even if they are moved to other locations around the body. In other words, they display "donor dominance", regardless of whether or not they're located in an area of edema, tension, poor blood supply, etc."

That's very clear to everyone Bryan!

According to you, the pre-existing growth rate of androgen dependant follicles is maintained when transplanted to other areas, quote again "they display "donor dominance", regardless of whether or not they're located in an area of edema, tension, poor blood supply, etc."

You clearly say regardless of "ANY" other factor, hence the etc in your claim!

You certainly "DID NOT" give yourself the "get out clause" in your original claim, that you are so desperate to find now!

You are even trying to make mechanistic distinctions now, between the process of androgen growth restriction of follicles, and androgen growth increases in follicles. Quote:

"Yes, that's also pretty much correct, although those "other" follicles aren't "androgen dependent" in the same way as the follicles in the first case"

Yet another different mechanism Bryan? Ockham would rap your knuckles with a ruler for that one!

In your original claim you said quote:

" which proved that hair follicles continue to grow (or go bald, for that matter), even if they are moved to other locations around the body"

Grow "OR" go bald! You didn't claim any difference "then" in donor dominance did you!



So explain the "differences" you "NOW" claim, and how the one androgen effect prevents outside effects, whilst the other allows these??


S Foote.

 

[Bryan]

Well Bryan, your own words on the subject in the link i posted clearly demonstrate my point here.

Quote (again!)

"All of these oddball theories were soundly refuted with the advent of modern hair transplantation, which proved that hair follicles continue to grow (or go bald, for that matter), even if they are moved to other locations around the body. In other words, they display "donor dominance", regardless of whether or not they're located in an area of edema, tension, poor blood supply, etc."

That's very clear to everyone Bryan!

According to you, the pre-existing growth rate of androgen dependant follicles is maintained when transplanted to other areas, quote again "they display "donor dominance", regardless of whether or not they're located in an area of edema, tension, poor blood supply, etc."

You clearly say regardless of "ANY" other factor, hence the etc in your claim!

You certainly "DID NOT" give yourself the "get out clause" in your original claim, that you are so desperate to find now!

Yes, that's all basically correct, although I will add one small but important detail which you're overlooking: it's the specific growth effect of THE ANDROGENIC STIMULATION ITSELF which is maintained, regardless of the location to which a hair follicle is transplanted. With that additional critical detail as a note of further explanation, I stand by what I said before. So what exactly is the objection you have with that?

You are even trying to make mechanistic distinctions now, between the process of androgen growth restriction of follicles, and androgen growth increases in follicles. Quote:

"Yes, that's also pretty much correct, although those "other" follicles aren't "androgen dependent" in the same way as the follicles in the first case"

Yet another different mechanism Bryan? Ockham would rap your knuckles with a ruler for that one!

You are totally confused, Stephen. I'm not talking about different MECHANISMS, I'm talking about different RESPONSES to androgenic stimulation, from one follicle to another.

In your original claim you said quote:

" which proved that hair follicles continue to grow (or go bald, for that matter), even if they are moved to other locations around the body"

Grow "OR" go bald! You didn't claim any difference "then" in donor dominance did you!

You seem confused, and I'm not sure what you mean. I stand by what I've been saying for years: when balding hair follicles are transplanted to other areas of the body, they continue to go bald. When healthy (growing) hair follicles are transplanted to other parts of the body, they continue to grow and survive.

So explain the "differences" you "NOW" claim, and how the one androgen effect prevents outside effects, whilst the other allows these??

The only additional effect to be acknowledged here is that the recent Korean experiment seems to indicate that there ARE additional influences on the growth of hair follicles that depend to some extent on their location in the body; however, those are INDEPENDENT of the powerful influence of androgens. The putative increase of body hair length that we seem to get when those follicles are transplanted to the scalp is separate from the effect of androgenic stimulation. Furthermore, no such effects are able to stop the balding of male pattern baldness hair follicles, regardless of where they are transplanted. They keep right on going bald, pretty much on schedule, wherever they are moved.

Capiche?

 

[S Foote.]

Well Bryan, your own words on the subject in the link i posted clearly demonstrate my point here.

Quote (again!)

"All of these oddball theories were soundly refuted with the advent of modern hair transplantation, which proved that hair follicles continue to grow (or go bald, for that matter), even if they are moved to other locations around the body. In other words, they display "donor dominance", regardless of whether or not they're located in an area of edema, tension, poor blood supply, etc."

That's very clear to everyone Bryan!

According to you, the pre-existing growth rate of androgen dependant follicles is maintained when transplanted to other areas, quote again "they display "donor dominance", regardless of whether or not they're located in an area of edema, tension, poor blood supply, etc."

You clearly say regardless of "ANY" other factor, hence the etc in your claim!

You certainly "DID NOT" give yourself the "get out clause" in your original claim, that you are so desperate to find now!

Yes, that's all basically correct, although I will add one small but important detail which you're overlooking: it's the specific growth effect of THE ANDROGENIC STIMULATION ITSELF which is maintained, regardless of the location to which a hair follicle is transplanted. With that additional critical detail as a note of further explanation, I stand by what I said before. So what exactly is the objection you have with that?

http://www.hairlosshelp.com/forums/mess ... &forumid=1[/url]

Remember Bryan, you questioned the relevance of the androgen level influence in that study yourself! :wink:

It really doesn't matter what we argue about on these forums. In my opinion the scientific issues around hair transplantation have traditionaly suffered, because of the vested interests of the transplantation industry.

There are many experiments that could be done to finally resolve these issues, and time will tell.

S Foote.

 

[Bryan]

You are totally confused, Stephen. I'm not talking about different MECHANISMS, I'm talking about different RESPONSES to androgenic stimulation, from one follicle to another.

My point "exactly" Bryan!

The claim you have made in the past and again here, is that "each" follicle has it's own "built in" response to androgens. The current theory claims that there are many different growth rate changes in follicles, in a "direct" response to androgens. You don't even claim the level of androgens is important, just the programing within the follicle itself.

Oh, I'm not saying that the level of androgens isn't important AT ALL, Stephen, I just think that the qualitative response to androgens (as opposed to the quantitative response) is probably a more significant factor, because of the wide range of responses to androgens that extend all the way from "stimulating" to "neutral" to "suppressive". At the very least, I personally am much more interested in that different qualitative response. I get kind of tired of it when posters on hairloss sites talk about nothing but levels of androgen receptors, levels of 5a-reductase inhibition, etc.

I will freely admit, though, that the information we're getting nowadays on the importance of androgen receptor polymorphisms to hairloss seems to support the idea that levels of androgenic stimulation are indeed the primary factor in male pattern baldness, at least with our current treatment methods. But that's only because we have no way (yet) to alter that qualitative response deep inside hair follicles. All we can do presently is lower the intensity of androgenic stimuli that they get.

This again is the whole claim made by donor dominance. The growth rate of the follicles in response to androgens, whatever that may be, is "locked" by the genetics of individual follicles.

Exactly! You've hit the nail on the head!

This is the very basis of the current theory, the growth rate whatever that is is "maintained" when transplanted to other areas!

The growth rate from androgenic stimulation is maintained, not necessarily other growth factors. Now we've seen some evidence that there are indeed other factors which seem to be able to somewhat alter growth rates of transplanted hair follicles, in some circumstances.

The donor domonance theory is just that Bryan, "donor doninance prevails". :roll:

Yes. As far as the effect of androgens is concerned.

But it just doesn't because the growth of alledged androgen dependant hair from the body, "significantly" changes when transplanted to the scalp!

But that's due to other factors than androgens.

You just can't have it both ways Bryan! You can't claim donor dominance "BECAUSE" of no growth change, then add on "other factors" when there "IS" a growth change ! :freaked:

I'm not trying to "have it both ways", Stephen. I'm simply saying that the effect of androgens on hair follicles is indeed donor dominant, but other things can affect hair growth, too. For example, everybody knows that chemotherapy for cancer very frequently causes all your hair to fall out! Are you going to try to claim that THAT disproves donor dominance, just because it affects ALL hairs, even transplanted ones?? :wink:

The only additional effect to be acknowledged here is that the recent Korean experiment seems to indicate that there ARE additional influences on the growth of hair follicles that depend to some extent on their location in the body; however, those are INDEPENDENT of the powerful influence of androgens. The putative increase of body hair length that we seem to get when those follicles are transplanted to the scalp is separate from the effect of androgenic stimulation. Furthermore, no such effects are able to stop the balding of male pattern baldness hair follicles, regardless of where they are transplanted. They keep right on going bald, pretty much on schedule, wherever they are moved.

No Bryan, that is just not a scientific argument!

Refer to what i said above, you cannot make a claim for donor "dominance" when there is "NO" change, then try to claim this still stands when there "IS" a change! :roll:

Sure I can do that, because it's the truth. The Korean body hair transplant experiment showed what was apparently a PERMANENT small offset of extra growth when body hair follicles were transplanted to the scalp, which shows that it has nothing to do with a gradual, steady, degenerative process like balding in which hair follicles eventually wither away and disappear altogether (like in the Nordstrom study). So you're attempting to compare two entirely different things, in what I consider to be a disingenuous attempt to discredit the very soundly proven concept of donor dominance. And again, that's donor dominance as it very specifically pertains to the response to androgens.

Apart from that the BHT results and that Korean study, there is that mouse study.

http://www.hairlosshelp.com/forums/mess ... &forumid=1

Remember Bryan, you questioned the relevance of the androgen level influence in that study yourself! :wink:

Let's be very precise here: I didn't question the relevance of the androgen level in that study, I questioned the androgen level. Period. Full stop. In other words, androgen levels weren't even reported in that study, so we can't draw any conclusions one way or the other.

 

[docj077]

Is it absurd to not think that perhaps all hair does indeed have an intrinsic growth rate, but is also highly susceptible to outside influences that are present within the tissue in which the hair is located.

It is obvious that hair (even so-called androgen dependent hair) does not require androgens for growth as their intrinsic growth rate is maintained in men with androgen insensitivity. In genotypic males with complete AIS, it is well known that they will still develop very minimal amounts of pubic and axillary hair. The growth and development of these secondary sexual characteristics is typically attributable to androgen action, but these follicles do have intrinsic activity and this activity is activated at puberty without the influence of androgens.

Partial or incomplete AIS will give the male with the syndrome more secondary hair or even hair that appears to be sexually normal.

Obviously, their is an intrinsic process in hair that is activated at puberty and androgens potentiate the effects of this process as you go from having minimal hair growth without the action of androgens (yet there is still growth) to increasing hair growth proportionally to the androgen increase and the actual allowed action of androgens.

If the same holds true for hair follicles in the scalp (which it likely does as they originate from the same embryological tissue), then a person with androgen hypersensitivity at the level of the hair follicle will overcome the intrinsic activity of the follicle, move it beyond growth, and encourage the surrounding tissue to cause growth inhibition to prevent the pro-growth conditions that are created. The rate of growth and the diameter of the hair shaft should be directly related to how far the tissue surrounding the hair follicle can increase follicular growth beyond the intrinsic activity of the follicle. The environmental androgen concentration should be directly linked to the amount of five alpha reductase in the surrounding tissue and the lack of anti-growth molecules and tissue.

There is no physiological reason for scalp hair to grow longer and for a greater duration other than the influence of extrinsic growth promoting factors that exist apart from the keratinocytes within the follicle. These factors are obviously not found within the skin away from the scalp or they are inhibited within the skin, but maintained in areas of post-pubescent hair growth.

There are obviously numerous other pathways that are involved in hair growth inhibition in male pattern baldness. Simply using androgens as an excuse really is flawed science. They are doing what they're supposed to do. It's the downstream response that is the problem.

 

[michael barry]

Doctor,

Could you elaborate on that downstream response in layman's English as much as possible.

Im assuming we get to TGF-beta slowing follicle growth, hyperkeratinization, and an immune response, but Ive never seen a step-by-step rendering of your thoughts.........................

 

[docj077]

Doctor,

Could you elaborate on that downstream response in layman's English as much as possible.

Im assuming we get to TGF-beta slowing follicle growth, hyperkeratinization, and an immune response, but Ive never seen a step-by-step rendering of your thoughts.........................

Well, I don’t know a whole lot about the process, but I’ll try to post some of my thoughts.

male pattern baldness does seem to be the result of single nucleotide mutation in the androgen receptor that creates a missense mutation. This results in abnormally functioning androgen receptor protein. Normally, the androgen receptor binds to the androgen receptor creating a complex. This complex normally binds with another complex creating a dimer that then acts as a transcription factor in the nucleus and promotes the transcription of genes such as TGF-beta and IGF-1.

However, in male pattern baldness, the androgen receptor seems to be hyperfunctional and the response is inappropriate. This defective androgen receptor appears to be present on the dermal fibroblasts and dermal papillae cells.

The consequences of TGF-beta overproduction can be shown by the following charts:

In the above chart, TGF-beta functions to decrease Wnt and Beta-catenin signaling through the inhibitory molecule TAK1. By removing Wnt and Beta-catenin signaling you essentially decrease follicular morphogenesis and inhibit the proper formation of the hair shaft structure. Proper hair cycling is effectively inhibited.

You'll also notice that TNF and IL-1 play a part in this process, as well. They are acute phase reactants and partially responsible for the immune response as their production is directly influenced by inflammation. TNF-alpha actually functions to downregulate the TGF-beta receptor response. TNF-alpha could possibly be more important than TGF-beta in the process, but we'll just have to wait and see what the research ends up showing us.

Lastly, you'll notice that TGF-beta influences the production of NF-kappaB. This molecule is involved in the pro-fibrotic response and is even responsible for positive feedback to increase TGF-beta production.

There are other molecules produced and other molecules inhibited. The following website demonstrates these molecules and their function:

http://physrev.physiology.org/cgi/conte ... 1/1/449/T3

The TGF family of molecules is also inhibited by the actions of SMAD-7. The following chart demonstrates this phenomenon:

SMAD-7 is known to promote the transformation of hair follicles into sebaceous units.


Also important, is the realization that TGF-beta not only inhibits proper hair cycling, but it also promotes keratinocyte apoptosis and decreases collagenase production in the extracellular matrix promoting collagen deposition and perifollicular fibrosis.

Lastly, we come to IGF-1. This molecule is normally produced and has an intrinsic function, but it is quite likely that IGF-1 production is increased with androgen exposure. The function of IGF-1 is pro-proliferative and anti-apoptotic. The problem it will inevitably cause will be an increase in keratinocyte production locally, which will result in hyperkeratinization. This is a process that is countered by the increase in TGF-beta production and in fact it is quite likely that the increase in TGF-beta production is the physiological solution to the hyperkeratinization and prolonged life of keratinocytes that results from IGF-1.

TGF-beta is also a chemotactic factor which means it draws immune cells into the peripheral tissues. However, it is not pro-proliferative. This is quite likely the reason why we see a lymphocytic infiltrate in some men with male pattern baldness along an autoimmune component.


I don’t know if any of that made sense and it’s probably not in layman’s terms, but those are my current thoughts on the subject. Overall, I'm finding that the molecular basis of hair loss is quite a mess right now. I still have found no evidence for contact inhibition as I can't find a ligand that would adequately explain such a process.

 

[S Foote.]

Bryan.

I will make this short as i haven't much time tonight.

Of course there are lot's of other factors that can and do effect hair growth. But the donor dominance claim in transplantation does not make any such allowences!

If as you now claim, other factors can change the growth of so called androgen responsive follicles, yet remain androgen dependant for "most" of it's growth characteristics, the next question is obvious?

How do you "KNOW" if it's another factor causing the growth change, or a change in the androgen control? How can you measure which factor is causing the change?

You just can't!

You are now saying that so called androgen dependant body hair can have it's androgen growth "control" overuled by external factors.

In your original claim about donor dominance, you quoted the case of male pattern baldness follicles transplanted to other areas retaining their growth rate as proof of your donor dominance argument.

Suppose i had said then that those male pattern baldness follicles "would" have increased their growth "IF" they had recieved other outside influences, that overuled the androgen effect you claimed?

You would have jumped on me instantly!

But now you want me to accept just this kind of argument :wink:

It is the current theory you support Bryan that is the problem you have here. My theory accepts external influences, yours just doesn't!

S Foote.

 

[S Foote.]

Whats up "Doctor"?

Why have you not cleared up the issue as to if you are a genuine Doctor or not? Here's a puzzle for you while you are thinking about it.

You claim some kind of faulty androgen receptor status as being the cause of male pattern baldness?

The in-vitro tests are often quoted as proof of the androgen action in male pattern baldness, as being "right there" within the follicles themselves. But because of the culturing process itself. the follicles cells used in these tests loose the ability to produce androgen receptors.

I had links to specific studies that stated this, but i lost these recently (computer problems). Perhaps Michael can help with these links.

Because of this, the samples in in-vitro tests are artificialy seeded with androgen receptors.

So are you trying to tell us that the researchers are seeding the cultures with "faulty" androgen receptors??

Also, you don't need to find any particular ligand to know that contact inhibition prevents the multiplication of "ANY" normal cell line, when there is no space for this. This is basic multicellular phisiology. The only cells that do "not" respond to contact inhibition are cancer cells, hence their ability to invade other tissues.

S Foote.

 

[docj077]

Whats up "Doctor"?

Why have you not cleared up the issue as to if you are a genuine Doctor or not? Here's a puzzle for you while you are thinking about it.

You claim some kind of faulty androgen receptor status as being the cause of male pattern baldness?

I don't claim this. There are many known AR gene polymorphisms including: the (CAG)n trinucleotide repeat, the (GGC)n trinucleotide repeat, and the R726L single nucleotide polymorphism. The defect in the androgen receptor appears to be a single nucleotide polymorphism. There are also co-receptor mutations that are well known and associated with male pattern baldness.

I see that you still lack appropriate forum manners. You know that I'm not a doctor. I'm a medical student. Big difference, but that doesn't discredit my opinion as I have many years of research experience combined with clinical experience. I always forget what your credentials are, but I'm sure that you'll remind us all of your incredible education and unparalleled research skills.

The in-vitro tests are often quoted as proof of the androgen action in male pattern baldness, as being "right there" within the follicles themselves. But because of the culturing process itself. the follicles cells used in these tests loose the ability to produce androgen receptors.

If this is true, then the hair follicles would lose more than just the ability to produce androgen receptors. Either transcription or translation would have to be inhibited cell-wide and if it simply a product that degrades protein, then all cellular processes would be inhibited. To expect any sort of results from such studies that use the culturing method you seem to be mentioning would be foolish at best.

The alternative is that the transportation machinery of the cell is somehow disrupted. But, once again, that would skew any results that are obtained using such a culturing method as one would expect inappropriate intracellular protein targeting.

I had links to specific studies that stated this, but i lost these recently (computer problems). Perhaps Michael can help with these links.

I would enjoy reading them. I don't believe you, but I'd enjoy reading them.

Because of this, the samples in in-vitro tests are artificialy seeded with androgen receptors.

So are you trying to tell us that the researchers are seeding the cultures with "faulty" androgen receptors??

I think we need to review the biochemistry on this one. The androgen receptor has hydrophilic groups within it. There is no way that it can pass through the hydrophobic cellular membrane to make its way to the nucleus. It's a big protein with multiple domains. Still, I'd like to read any information you might have on this. I don't believe it, but I'll still read it.

Not only would the added androgen receptor have to make across a physiologically impossible barrier, but they also need to have dimerized with androgen attached before they can adequately carry out transcription of their targeted genes.

Normally, the androgen receptor is cytoplasm-bound and it must translocate into the nucleus to carry out its function. This process is carried out by the f-actin cross-linking protein Filamin. If the intracellular structure of the cell is so interrupted so as to prevent normal cellular processes, then one can guarantee that the androgen receptor is not going to make it to the nucleus no matter what you do.

Also, you don't need to find any particular ligand to know that contact inhibition prevents the multiplication of "ANY" normal cell line, when there is no space for this. This is basic multicellular phisiology. The only cells that do "not" respond to contact inhibition are cancer cells, hence their ability to invade other tissues.

S Foote.

Mr. Foote, you and I both know that contact inhibition requires a specific ligand to induce the inhibition. I've asked you to find some research on the specific molecule, but you have not yet helped me out. I've looked everywhere and I can find no evidence of contact inhibition and I still can not find any evidence of lymphedema histologically. There simply is no spongiosis and no evidence of lymphatic obstruction. I also have yet to find clear evidence for valvular insufficiency localized within the lymphatics of the scalp. You have to help me out here, because somebody needs to be helped as you're not helping yourself. Plus, one must consider that there is a very real possibility that normal cellular function within the hair follicle requires intercellular contact.