Study: Propecia Responders and Non-Responders

[S Foote.]

Well Bryan, you like to claim that i have no proof for what i propose, but neither does the current theory! At least i have some precidents!

WHACK goes the ruler!

That's spelled "precedent", not "precident". I wish I had a buck (or a quid) for every time you use that word. You use it in contexts that don't even really make sense.

http://www.itzan.com[/url]
(Mexico)"

Just what qualifies you to stand in judgement on the opinions of professional scientists? Seriously Bryan, i think people who read your posts should know what makes your opinion as important as you think it is! So please tell us all the basis of your expertise?

The LNCaP cell line `flip' does `NOT' provide a `precedent' for your theory for a number of reasons, that have been explained to you. Plus you just can't have it both ways Bryan. First you try to tell us that prolonged exposure `TO' androgens is needed to cause cell growth restriction. Now you try to tell us that the direct `OPPOSITE' of androgen deprevation proves your point!

Why don't you contact the authors of that study for their opinions on your `new' theory?

By the way, i have asked you this before, but you have avoided the issue. Please explain the mechanisms of how the `direct theory', accounts for the recognised immunology in male pattern baldness, and the profound sweating efficiency changes?

S Foote.

 

[Old Baldy]

You think ageing itself causes follicles to flip-flop in their response to androgens? Why would that occur?

No Bryan, just normal ageing hair loss like you alluded to in another forum.

"And maybe the gradual declines in haircounts are just due to normal ageing, and not a so-called "tolerance" to finasteride! "

Bryan

Not saying anything more than that.

Btw HairLossTalk.com, they are VERY interesting discussions aren't they. Even if I don't understand one-half of what they are saying.


Oh, I forgot to paste this link for this study that that talks about androgens, etc. (Bryan and Stephen already know of this study, but for the rest of us that don't, it's pretty interesting reading.)

http://edrv.endojournals.org/cgi/content/full/21/4/347

This part of the study is where Stephen and Bryan, I think, have a MAJOR bone of contention: (Doctors just don't know the "secret" yet.)

Hence, it is possible that differences in local androgen metabolism could account for the different clinical presentations of androgenetic alopecia between genders. Nonetheless, it is still unclear whether these differences are due to increased local clearance of androgens (via conversion to estrogens) or from a direct estrogen effect. In fact, some investigators have suggested that estrogens can directly cause scalp hair loss by altering the anagen-telogen rate (40).

Now this study deals with females alot but I think you could draw analogies with men also by substituting estrogen with androgen, etc.? Correct me if I am way off base here Stephen and Bryan. (Just trying to learn.) Or maybe estrogens and androgens are similar enough to make direct analogies?

 

[S Foote.]

You think ageing itself causes follicles to flip-flop in their response to androgens? Why would that occur?

No Bryan, just normal ageing hair loss like you alluded to in another forum.

"And maybe the gradual declines in haircounts are just due to normal ageing, and not a so-called "tolerance" to finasteride! "

Bryan

Not saying anything more than that.

Btw HairLossTalk.com, they are VERY interesting discussions aren't they. Even if I don't understand one-half of what they are saying.


Oh, I forgot to paste this link for this study that that talks about androgens, etc. (Bryan and Stephen already know of this study, but for the rest of us that don't, it's pretty interesting reading.)

http://edrv.endojournals.org/cgi/content/full/21/4/347

This part of the study is where Stephen and Bryan, I think, have a MAJOR bone of contention: (Doctors just don't know the "secret" yet.)

Hence, it is possible that differences in local androgen metabolism could account for the different clinical presentations of androgenetic alopecia between genders. Nonetheless, it is still unclear whether these differences are due to increased local clearance of androgens (via conversion to estrogens) or from a direct estrogen effect. In fact, some investigators have suggested that estrogens can directly cause scalp hair loss by altering the anagen-telogen rate (40).

Now this study deals with females alot but I think you could draw analogies with men also by substituting estrogen with androgen, etc.? Correct me if I am way off base here Stephen and Bryan. (Just trying to learn.) Or maybe estrogens and androgens are similar enough to make direct analogies?

I think the main thing to remember is that we are looking for something that is changing the inherent growth response in follicle cells. I am arguing that this is the important thing, and `not' what may or may not subsequently effect these changed cells, including androgens.

There are two studies that i would argue further support the idea that contact inhibition in-vivo, is the mechanism of change, and this induces a `changed' response to androgens in-vitro.

The first study indicates that TGF Beta 1 is the mediator in DP cells growth response signaling. The second shows that contact inhibition and the TGF Beta 1 pathways are connected.

I haven't got time to go into this tonight, but it is clear that TGF Beta 1 can `lock' contact inhibited cells in that condition. Hence they would show a `changed' growth response in-vitro.

S Foote.

__________________________________________


Nippon Ronen Igakkai Zasshi. 2004 Nov;41(6):598-600.


Itami S.

Department of Dermatology, Course of Molecular Medicine, Graduate School of Medicine, Osaka University.

Hair follicles are composed primarily of epithelial and dermal components that develop from embryonic ectoderm and mesoderm respectively. The hair growth cycle is coordinated with complex processes that are dependent on the interactions of epithelial and dermal components. Beard and frontal scalp dermal papilla cells (DPCs) show the characteristics of androgen target cells. These DPCs expressed androgen receptor and type II 5alpha-reductase mRNA. To understand the mode of androgen action in human hair follicles, we developed an in vitro co-culture system using DPCs and follicular keratinocytes. Androgen significantly stimulated the proliferation of keratinocytes co-cultured with beard DPCs, suggesting that these DPCs produce androgen-dependent diffusible growth factors. Insulin-like growth factor-I (IGF-I) was identified as one of the androgen dependent paracrine growth factors from beard DPCs. On the other hand, we identified inhibitory roles of androgen on the growth of keratinocytes co-cultured with DPCs from human balding frontal scalp, when DPCs were transfected with the AR expression vector. This inhibitory effect was mediated by TGF-beta1 from the DPCs. Minoxidil and Finasteride were recently introduced for the treatment of androgenetic alopecia in Japan, and TGF-beta1 is the next target for innovative treatment.

Publication Types:
Review
Review, Tutorial

PMID: 15651368


______________________________________

Cell cycle arrest in G0/G1 phase by contact inhibition and TGF-beta 1 in mink Mv1Lu lung epithelial cells.

Wu F, Buckley S, Bui KC, Yee A, Wu HY, Liu J, Warburton D.

Department of Surgery, Children's Hospital of Los Angeles, California, USA.

We postulated that contact inhibition and transforming growth factor (TGF)-beta 1 may target the same molecules to negatively regulate the Mv1Lu cell cycle in G0/G1. Both contact inhibition and TGF-beta 1 suppressed the expression of a 45-kDa protein (p45); cyclins D2 and B1; cyclin-dependent protein kinase (Cdk)-4, Cdc-2, and Cdc-2-associated activity; and the phosphorylation of retinoblastoma tumor-suppressor protein (pRb) but did not affect the expression of cyclins D1, E, and A or the expression of Cdk-2 and Cdk-5. Expression of p45 reappeared 12 h after release from contact inhibition and 6-8 h after release from TGF-beta 1, while TGF-beta 1 prevented release from contact inhibition and maintained suppression of both p45 and cyclin D2. Additionally, cyclin D2 phosphorylation and its associated kinase activity were strongly inhibited by contact inhibition and TGF-beta 1. Thus suppression of p45, cyclin D2/Cdk-4, and cyclin B1/Cdc-2 expression and/or activities is targeted both by contact inhibition and by TGF-beta 1 and may define common mechanisms through which these negative growth signals are integrated.

PMID: 8967524 [PubMed - indexed for MEDLINE]

 

[Bryan]

You think ageing itself causes follicles to flip-flop in their response to androgens? Why would that occur?

No Bryan, just normal ageing hair loss like you alluded to in another forum.

"And maybe the gradual declines in haircounts are just due to normal ageing, and not a so-called "tolerance" to finasteride! "

Bryan

Not saying anything more than that.

What Stephen and I have been discussing in these last few posts is not hairloss per se, but the fact that scalp hair follicles (at least in stumptailed macaques) apparently go from being relatively unaffected by androgens PRIOR to puberty, to being suppressed by them AFTER puberty. The current bone of contention is the exact mechanism behind that phenomenon.

Bryan

 

[S Foote.]

You think ageing itself causes follicles to flip-flop in their response to androgens? Why would that occur?

No Bryan, just normal ageing hair loss like you alluded to in another forum.

"And maybe the gradual declines in haircounts are just due to normal ageing, and not a so-called "tolerance" to finasteride! "

Bryan

Not saying anything more than that.

What Stephen and I have been discussing in these last few posts is not hairloss per se, but the fact that scalp hair follicles (at least in stumptailed macaques) apparently go from being relatively unaffected by androgens PRIOR to puberty, to being suppressed by them AFTER puberty. The current bone of contention is the exact mechanism behind that phenomenon.

Bryan

Yes, thats well put Bryan.

I would like your opinions on the relevance to this debate, of the two studies i refer to above Bryan. There are some other studies i also think are relevant to the in-vitro situation. I have a few family issues to deal with, so i don't have much spare time today or tomorow.

I might post these in a new thread later in the week.

S Foote.

 

[Bryan]

The LNCaP cell line `flip' does `NOT' provide a `precedent' for your theory for a number of reasons, that have been explained to you.

And I've explained to YOU that it's pretty clear-cut: withholding androgens from them eventually causes them to flip-flop in their response to androgens. There's no use trying to put your own "spin" on it, Stephen. It's clearly analogous to what happens with scalp hair follicles, even if we don't know the exact mechanisms of why it happens in either one of those cases.

Plus you just can't have it both ways Bryan. First you try to tell us that prolonged exposure `TO' androgens is needed to cause cell growth restriction. Now you try to tell us that the direct `OPPOSITE' of androgen deprevation proves your point!

You're being quite naive. It's not at all unusual for different tissues to have different responses to hormones. For example, you may have seen my post a couple of weeks ago over on HLH where I explained to someone that androgens UPregulate the production of androgen receptors in rat neural tissue, but they DOWNregulate them in human scalp hair follicles. Your complaint that the response to androgens (or the LACK of androgens) is different in hair follicles and LNCaP CANCER cells is beyond silly! You cannot make the simple-minded assumption that they ought to be the same, therefore if they're different, that supports your theory! :wink: The only important point here that you need to acknowledge is that prolonged exposure to androgens (or a prolonged ABSENCE of androgens) is apparently able to induce a change (SOME kind of change) in the subsequent response to those same androgens in two different kinds of tissues, for whatever reason(s).

By the way, i have asked you this before, but you have avoided the issue. Please explain the mechanisms of how the `direct theory', accounts for the recognised immunology in male pattern baldness, and the profound sweating efficiency changes?

Can you specify exactly what you mean by the "recognized immunology" in male pattern baldness? As for the sweating changes, I've read that study you're interested in (the one on hairloss and sweating changes), and it seems like a plausible theory to me. But that doesn't really have anything to do with the "direct theory", as far as I can tell. But I'm sure YOU have your own spin on that! :wink:

Bryan

 

[Bryan]

There are two studies that i would argue further support the idea that contact inhibition in-vivo, is the mechanism of change, and this induces a `changed' response to androgens in-vitro.

The first study indicates that TGF Beta 1 is the mediator in DP cells growth response signaling. The second shows that contact inhibition and the TGF Beta 1 pathways are connected.

I don't have a problem with either one of those statements, except I wouldn't say that TGF Beta 1 is THE mediator in DP cells. I would say that it's probably ONE of numerous factors that are affected by androgens. There's probably a veritable "alphabet soup" of such hormones and growth factors! :wink:

I haven't got time to go into this tonight, but it is clear that TGF Beta 1 can `lock' contact inhibited cells in that condition. Hence they would show a `changed' growth response in-vitro.

I think you're inferring too much from that abstract. Please explain why you think that it "locks" them into that condition. I don't think that's what they're saying...

Bryan

 

[Old Baldy]

Bryan and Stephen: I understand, you are both looking for that "trigger". They've been looking for that for many years before we were born. It's proven to be VERY elusive.

I guess the problem I'm having with both of your theories is you are explaining what might initiate that "trigger" but not explaining what allows that susceptibility to the trigger to exist in the first place. (You know, if your follicles die only when you die than who cares.)

Now, I certainly don't expect you both to have definitive answers to why our bodies become susceptible to those triggers in the first place. That would be extremely unfair and arrogant on my part.

For some G** Da** reason our cellular structure changes to an extent that allows the trigger to occur in the first place. It's an "implant" initiated in the womb. Shutting off that "implant" is what we need. That's the "secret" in my layman's mind.

Can that genetic implant (expression) be "shut-off" once we are born. Of course it can. We just don't know how yet. But finding the answer takes a different path than you both are taking IMHO>

The most likely theory from what I've been reading, and as you both probably know is genetic. Why did that that genetic implant happen? I assume it was evolutionary/mutational.

But why evolutionary/mutational?

What would cause follicles before puberty to change in their response to androgens after puberty. Is it because androgens aren't produced before puberty to such an extent to cause problems?

Even so, why are those cells susceptible to androgen activity in the first place? What is that da** trigger. It happened in the womb Stephen and Bryan.

In the womb, something DNA wise, was input on those follicle genes to allow for male pattern baldness. What was that implant? Why did it happen? Why did Mother Nature allow that implant to occur? What mechanism caused that implant to occur? Was it mutational and, since it wasn't fatal, it was allowed to proliferate? Why do mutations occur. FOR EVOLUTIONARY TESTING PURPOSES. That's why.

Believe me, in my layman's mind, I do understand.

You see, stumptailed macaques (spelling?) are merely exhibiting the same characteristics we exhibit. So testing on them is informative. But what caused that trigger to exist in them?

What is it about our genetic make-up that allowed the scalp hair, for both men and women, to become sensitive to androgens or estrogens?

Are there other diseases or ailments that deal with the same type of trigger changes that allowed "flip flopping"? There has to be.

Guys, I understand and I also understand that if we unlock what causes these types of triggers we will cure alot more ailments than male pattern baldness.

What I'm saying is, until we know more about gene manipulation, we really won't have a cure for male pattern baldness. Please forgive me when I say you are both looking for answers in an area that won't give an answer. I'm sorry to say that and I don't mean any disrespect either. I think men like you (doctors and researchers alike) have basically proven that genetic manipulation is the only real answer?

You guys are trying to find the trigger by using "after effects" analysis IMHO. This is no criticizm because I don't have any solutions either. In fact, I have FAR less than you both do.

Your "after the trigger" treatments might go a long way towards keeping follicles alive until we die, but they won't ever find the secret IMHO.

I know I'm rambling but here's another example. Imagine you are looking at a firearm. Current solutions for male pattern baldness seem to take the path of putting a lock on the firearm's trigger in hopes of preventing it from "going off" and firing the cartridge. The true secret would be to start with a firearm that didn't have a trigger in the first place.

I worry that I will never know in my lifetime? Or will I?

http://www.hairtransplantation.com/adva ... grows.html

I know you guys know of this study but it appears they are getting beyond "after trigger" treatments and FINALLY starting to get to what forms that trigger in the first place. They haven't found the secret by a long shot but they're getting closer IMHO. They just haven't pierced that "initial genetic implant" bubble yet.

 

[Armando Jose]

Old Baldy wrote:

"I understand, you are both looking for that "trigger". They've been looking for that for many years before we were born. It's proven to be VERY elusive. "
I concur



"What would cause follicles before puberty to change in their response to androgens after puberty. Is it because androgens aren't produced before puberty to such an extent to cause problems? "

In my opinion, androgens are produced in the vacinity of pilosebaceous follicle also before puberty (*). In child's hair there is sebum, and therefore androgens. male pattern baldness is a very slow process, mainly in the first stages, where is the real "trigger" of this degenerative process.

BTW, a very interesting post.

Armando

(*) Specially for Bryan. I think that this reason is the same in the supossed "luxuriant" scalp hair in person with complete androgen insensitivity syndrome.

 

[S Foote.]

S Foote. wrote:
The LNCaP cell line `flip' does `NOT' provide a `precedent' for your theory for a number of reasons, that have been explained to you.

>Bryan wrote
And I've explained to YOU that it's pretty clear-cut: withholding androgens from them eventually causes them to flip-flop in their response to androgens. There's no use trying to put your own "spin" on it, Stephen. It's clearly analogous to what happens with scalp hair follicles, even if we don't know the exact mechanisms of why it happens in either one of those cases.<

S Foote. wrote:
Plus you just can't have it both ways Bryan. First you try to tell us that prolonged exposure `TO' androgens is needed to cause cell growth restriction. Now you try to tell us that the direct `OPPOSITE' of androgen deprevation proves your point!

>Bryan wrote
You're being quite naive. It's not at all unusual for different tissues to have different responses to hormones. For example, you may have seen my post a couple of weeks ago over on HLH where I explained to someone that androgens UPregulate the production of androgen receptors in rat neural tissue, but they DOWNregulate them in human scalp hair follicles. Your complaint that the response to androgens (or the LACK of androgens) is different in hair follicles and LNCaP CANCER cells is beyond silly! You cannot make the simple-minded assumption that they ought to be the same, therefore if they're different, that supports your theory! The only important point here that you need to acknowledge is that prolonged exposure to androgens (or a prolonged ABSENCE of androgens) is apparently able to induce a change (SOME kind of change) in the subsequent response to those same androgens in two different kinds of tissues, for whatever reason(s).<

____________________________________________________

But you are `entirely' missing the real point here Bryan.

The LNCap cell line experiences a flip flop reaction to androgens because they are `abnormal' cancer cells. There is again `no' precedent for `normal' cells to demonstrate this kind of `opposite' reaction to varying levels of androgens! It is the genetic changes induced by an outside influence, in this case the cancer, that makes this flip flop possible!!

What you are saying in respect of the flip flop in hair follicle cells, is that the presence of androgens is in itself CREATING genetic changes that `then' allow a flip flop in androgen response.

For your analogy with LNCap cells to be valid, exposure to androgens would have to be `inducing' the cancerous changes in these cells!! This is clearly not so, or we would `ALL' develope this kind of prostate cancer!

Don't you see the point here Bryan? It takes something other than androgens to `induce' the genetic changes necessary for cells to `flip' in their response to androgens!

I argue that prior contact inhibition in-vivo, can also `induce' the necessary genetic changes for a `flipped' in-vitro response to androgens. I use the LNCap cell example as a precedent for such a `flipped' reaction to androgens.

___________________________________________

S Foote. wrote:
By the way, i have asked you this before, but you have avoided the issue. Please explain the mechanisms of how the `direct theory', accounts for the recognised immunology in male pattern baldness, and the profound sweating efficiency changes?

>Bryan wrote
Can you specify exactly what you mean by the "recognized immunology" in male pattern baldness? As for the sweating changes, I've read that study you're interested in (the one on hairloss and sweating changes), and it seems like a plausible theory to me. But that doesn't really have anything to do with the "direct theory", as far as I can tell. But I'm sure YOU have your own spin on that! <

________________________________________

My theory doesn't have any `spin' Bryan, it doesn't need it! What a plausible theory is supposed to do is provide a cause and effect pathway to explain `all' the observations. I will describe how my theory explains these observations, then you can give us your explaination Bryan? I'am afraid your direct theory is `required' to explain the sweating changes, as these are integral to DHT related hair growth/loss! You cant just ignore what doesn't suit!

I think by now, most people know something about the inflammation component of male pattern baldness. The timeline is that follicle miniaturization tends to be followed by an immune infiltrate in the tissue around the follicles. There is an increased immune sensitivity in the individuals balding scalp, to general irritations or allergies. Over the longer term, fibrose tissue tends to form in the balding scalp.

This fibrose tissue around and below the follicles, creates a further restriction to the normal anagen enlargement we want. I can't get the link to work at the moment, but the respected researcher Dr Uno refered to this factor in one of his papers. This factor alone is yet `another' precedent for a role of normal contact inhibition in anagen follicle size.

It has been established that androgen related hair loss/growth, also has a profound effect on the sweating efficiency of the local tissue. Where androgens reduce hair growth (male pattern baldness), there is a significant increase in the local sweating capacity. Where androgens increase hair growth (beard). there is a significant reduction in the local sweating capacity. Unlike the situation in hair follicles, there are no changes in the size of the local sweat glands, or any other physical changes in these glands.

The Hydraulic theory explains this sequence of events easily, using `ONE' primary action of DHT.

I have argued that the `major' in-vivo effect of DHT on hair growth, involves DHT related changes in the local tissue fluid pressures. These changes alter the resistence to anagen follicle enlargement through normal contact inhibition.

So according to this, increased local tissue fluid pressures = reduced hair growth, and reduced local fluid pressures = increased hair growth.

In the balding scalp the increased fluid pressure, and therefore levels, that miniaturizes follicles through contact inhibition, will `ALSO' increase immune infiltrate, sensitivity, and ultimate fibrosis. This is already recognised in tissues subject to increased fluid levels in lymphedema. http://www.lymphoedema.org.au/index.htm

Sweat glands have no `pumping' mechanism, so they are just `bleeding' off fluid at the local tissue fluid pressure. The findings in this study, are predicted by the local fluid pressure changes of the Hydraulic theory. The theory predicts reduced sweating with increased hair growth and vice versa!! http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract

So the immunology and sweating changes in male pattern baldness, can be explained by the `SAME' fluid pressure changes according to `recognised' physiology!

The direct theory can't explain these things without adding complication. For example, the direct theory proposes a `mechanism' that directly effects cell growth, and follicle size. But there are no such changes in the sweat glands, so the direct theory needs another unrelated mechanism. Bad new's in terms of scientific validity!

Remember Bryan, we must not multiply entities unnecessarily! (Ockham's razor).

I will try to respond to the other posts tommorow, it's been a long hard day!

S Foote.

 

[Bryan]

Old Baldy: You kept referring to the "trigger" for hairloss, and you seem to be interested in the evolutionary explanation for it. There's a number of theories about that, including the one which Stephen evidently supports, which is that balding developed to help cool the brain. It seems as plausible to me as any other theory, but who knows for sure if it's correct?

Armando Jose: I don't understand the point of your post, and you still haven't explained your own theory. Try again.

Bryan

 

[Bryan]

But you are `entirely' missing the real point here Bryan.

The LNCap cell line experiences a flip flop reaction to androgens because they are `abnormal' cancer cells. There is again `no' precedent for `normal' cells to demonstrate this kind of `opposite' reaction to varying levels of androgens! It is the genetic changes induced by an outside influence, in this case the cancer, that makes this flip flop possible!!

Well, you've now come full-circle, Stephen! YOU were the one who originally brought up the case of the LNCaP cancer cells, in an attempt to bolster your theory by providing a "precedent" (cough) of how a change in the response to androgens can be provoked by some outside influence. So I pointed out to you that it was actually the LEVEL of the androgens themselves which provoked that change, so now you've made a complete U-turn by saying sorry, that example doesn't count after all, because they're just CANCER cells! You're completely transparent, Stephen! You can't have it both ways! :wink:

I argue that prior contact inhibition in-vivo, can also `induce' the necessary genetic changes for a `flipped' in-vitro response to androgens.

Well, you better get back to work and try to find a "precedent" for that. Something BESIDES those cancer cells! :wink:

As for the rest of your post about immunology: I don't really have much comment, except that I generally support what Dr. Proctor says about that part of balding: androgens may cause hair follicle cells to express antigens that draw the attention of the immune system. Your attempt to paint everything with a broad "edema brush" is no less speculative than any other theory.

Bryan

 

[Temples]

Hey Brian, what is your take on equol? I read an interesting article about it here:

http://www.stophairlossnow.co.uk/News/News185.htm

 

[Bryan]

I think the effects of equol should be very very similar to those of the 5a-reductase inhibitors like finasteride and dutasteride.

Bryan

 

[Armando Jose]

Old Baldy: You kept referring to the "trigger" for hairloss, and you seem to be interested in the evolutionary explanation for it. There's a number of theories about that, including the one which Stephen evidently supports, which is that balding developed to help cool the brain. It seems as plausible to me as any other theory, but who knows for sure if it's correct?

Armando Jose: I don't understand the point of your post, and you still haven't explained your own theory. Try again.

Nature is based in biology, there is not magical effects. Scalp hair is important to "insulating" the brain from cold and hot. Remember Napoleon's troops in Rusia. Evolution give us a unique and fantastic scalp hair.

My theory is that problems in sebum flow is the initial cause of common baldness. This aspect is reversible but, sadly, after there is another mechanism that make impossible to get back the hair lost (androgens, fibrosis, inflamatory process, inmunologic process, problems with stem cells, etc, etc). Please visit my web: http://www.againstalopeciaandbaldness.com where is the full text of my theory (Medical Hypotheses Journal)

Armando

 

[Old Baldy]

Guys, let me clarify something here. Finding treatments that prevent male pattern baldness from taking hold, after we have a genetic propensity to express it, are a fine way to go.

Bryan: Don't, for one minute, think that I disagree with your direct effect theory. That's what DHT does in my layman's opinion. I just think it might work in tandem with Stephen's type of evolutionary theory. That's all. Of course, if you get rid of the initial trigger, there is no need for any further prevention treatment. There would be nothing more to prevent.

Da** I wish I had gotten into this type of field for my life's work.

Bryan (and maybe Stephen also): You're about my age. You remember all the wacko remedies they touted when we were kids. It was ridiculous. We have come so far in understanding male pattern baldness in the last 40 years that I honestly believe there will be a cure. Whether it addresses the "before" or "after" effects of the trigger, it will be "cured" someday. I honestly believe that.

The evolutionary theory has to go beyond sebum and "cooling" IMHO. It has to address why some people have follicles that are insensitive to "DHT" and others have follicles that are sensitive to "DHT". (I put DHT in quotes to cover whatever hormones, chemicals, etc., causes the trigger to express itself. I think it is DHT, but whatever.) There has to be some genetic, DNA, type of reason why my follicles are more sensitive than a non-balding man's follicles are. There just simply has to be some DNA type of reason for this variance to occur in humans. In my layman's opinion, that's the "secret". :?

So find that cure guys!!! (I'm stupid to find it.)

 

[Bryan]

My theory is that problems in sebum flow is the initial cause of common baldness. This aspect is reversible but, sadly, after there is another mechanism that make impossible to get back the hair lost (androgens, fibrosis, inflamatory process, inmunologic process, problems with stem cells, etc, etc). Please visit my web: http://www.againstalopeciaandbaldness.com where is the full text of my theory (Medical Hypotheses Journal)

I took a quick look at your site, but your language is so confusing to me that I'm still not sure what your theory is. For example, I'm not sure what you mean by sebum "detention". I still don't know if you think sebum is GOOD or BAD for hair.

By the way, here's some information for you: hair doesn't adsorb sebum. Kligman and his colleagues demonstrated that in an exhaustive series of tests on shampoos a few years ago, so one of your fundamental premises is incorrect.

Bryan

 

[Bryan]

Bryan: Don't, for one minute, think that I disagree with your direct effect theory. That's what DHT does in my layman's opinion. I just think it might work in tandem with Stephen's type of evolutionary theory. That's all. Of course, if you get rid of the initial trigger, there is no need for any further prevention treatment. There would be nothing more to prevent.

What exactly do you mean by "initial trigger"?

The evolutionary theory has to go beyond sebum and "cooling" IMHO.

Why?

It has to address why some people have follicles that are insensitive to "DHT" and others have follicles that are sensitive to "DHT".

It's not an all-or-nothing proposition. The evolutionary pressure for thinning hair (whatever the correct explanation for it is, whether it's the "cooling" theory or something else) is just a TENDENCY, an INFLUENCE in that direction. Different individuals will be susceptible to balding in various degrees and gradations.

There has to be some genetic, DNA, type of reason why my follicles are more sensitive than a non-balding man's follicles are. There just simply has to be some DNA type of reason for this variance to occur in humans. In my layman's opinion, that's the "secret". :?

We don't know all the biochemical steps in the balding process yet, but maybe someday we will. But that's a separate issue from the evolutionary pressures which created the problem in the first place.

Bryan

 

[S Foote.]

S Foote. wrote:
But you are `entirely' missing the real point here Bryan.

The LNCap cell line experiences a flip flop reaction to androgens because they are `abnormal' cancer cells. There is again `no' precedent for `normal' cells to demonstrate this kind of `opposite' reaction to varying levels of androgens! It is the genetic changes induced by an outside influence, in this case the cancer, that makes this flip flop possible!!

>>Bryan wrote
Well, you've now come full-circle, Stephen! YOU were the one who originally brought up the case of the LNCaP cancer cells, in an attempt to bolster your theory by providing a "precedent" (cough) of how a change in the response to androgens can be provoked by some outside influence. So I pointed out to you that it was actually the LEVEL of the androgens themselves which provoked that change, so now you've made a complete U-turn by saying sorry, that example doesn't count after all, because they're just CANCER cells! You're completely transparent, Stephen! You can't have it both ways!<<

How can you possible read `THAT' into my argument Bryan????

It is quite obvious to everyone that androgens are `NOT' responsible for the way LNCap cells `ARE', the cancer process is!

You are trying to claim that androgens are `converting' follicle cells from being non responsive, to being `directly responsive to androgens. There is no precedent for this, simple!

I have not gone `full circle', or made any U turns Bryan! The LNCap cell `flip' response to androgens, supports my theory not yours!



S Foote. wrote:
I argue that prior contact inhibition in-vivo, can also `induce' the necessary genetic changes for a `flipped' in-vitro response to androgens.

>>Bryan wrote
Well, you better get back to work and try to find a "precedent" for that. Something BESIDES those cancer cells!<<

Between them, the two studies i posted above shows that my argument is valid Bryan.

From the first study:

" On the other hand, we identified inhibitory roles of androgen on the growth of keratinocytes co-cultured with DPCs from human balding frontal scalp, when DPCs were transfected with the AR expression vector. This inhibitory effect was mediated by TGF-beta 1 from the DPCs."

From the second study:

" Thus suppression of p45, cyclin D2/Cdk-4, and cyclin B1/Cdc-2 expression and/or activities is targeted both by contact inhibition and by TGF-beta 1 and may define common mechanisms through which these negative growth signals are integrated"

So, the in-vitro effect of a negative growth action of androgens on balding cells, is mediated through TGF-Beta 1. The same pathways of cell growth restriction, are also used by contact inhibition.

It is therefore likely that the growth restriction changes in genetic expression, `induced' in follicle cells by contact inhibition in-vivo, is simply being maintained by TGF-Beta 1 in-vitro. This is fully in line with what is seen in the in-vitro experiments!

This is a `real' precedent for what we `actually' see Bryan. I am still waiting for any genuine precedents for your theory?


>>Bryan wrote
As for the rest of your post about immunology: I don't really have much comment, except that I generally support what Dr. Proctor says about that part of balding: androgens may cause hair follicle cells to express antigens that draw the attention of the immune system. Your attempt to paint everything with a broad "edema brush" is no less speculative than any other theory.<<

So you admit the current theory just can't explain the observations!

You say " Your attempt to paint everything with a broad "edema brush" is no less speculative than any other theory"

How can a theory that explains the observations in male pattern baldness, be just as speculative as a theory that can't explain the observations? It's no good having a go at me Bryan, i didn't make the scientific rules!! :wink:

S Foote.

 

[Armando Jose]

To Old Baldy and Bryan

To Old Baldy;
Certainly scalp hair is more important for us, not only for cooling. Possibly amazing new discoveries bring out the future investigations, more even that the studies of Paus and others. Also, generalizing, the life is not consistent without hair; the persons with alopecia universalis also have miniaturized hairs and suffer from serious immunological ailment.
In my opinion, there is not any genetic reason to loss certain hairs over the scalp, moreover when the hairs are asynchronous and independents, and then possibly all equals. I fail to meet any reference regarding the difference between healthy hairs, even in men or women.
You are confident that in the future there will be a solution for alopecia, but nowadays exist this possibility with hair transplant. But if you refer to induce the growth “in situ†a new hair, before there is a long way: understand completely the exact biologists mechanism that occur in the embrionary phase. This is complex in extreme; even the timing of biological signals could be crucial. If we break the equilibrium, serious side effects could appear, as indicate the research of Elaine Fuchs. Then, before bring to light a cure for baldness, there will be a good preventive method.


To Bryan:
Please, excuse for my English.
“Sebum is good or bad?†Neither good nor bad, sebum is necessary for hair. You know, pilosebaceous system.
“The hair doesn’t adsorb sebumâ€. Perhaps adsorb isn’t the best form to describe the process. Sebum is located over all the surface of hair shaft and the source, naturally, is the sebaceous gland. How it gets there?. The experiments (*) don’t corroborate “the obvious idea that the sebum, excreted into the follicular canal, simply spreads up the hair shaft and uniformly coats it. It seems an inescapable conclusion that the hairs become greased by mechanical transfer, from the scalp surface to the hairs, and from hair to hair.,…, The hair acquires sebum by direct contact. The dispersal of sebum from the surface would be facilitated by combing and brushing, by wearing a hat, by rubbing the fingers through the hair, etc. Resilient, easily bendable thin hair would have a greater chance of contacting sebum than straight, stiff, widely-spaced hairs. Refatting of the hair is thus complex and will vary greatly from individual to individual.â€
The last sentence sounds me as a possible genetic factor, doesn’t it?. The genetic trait determines the density, thickness, colour and type the hair, including his disposition over the scalp.
In the other hand, sebum is secreted continuously. Passing the time, the sebum change physical, chemical and biologically, due to his high inestability. Then also it’s necessary eliminate the sebum continuously. I am referring at “detention of sebum flow†when this process is blocked anyway.

Moreover, in the same study appears: “Regarding efficiency, all shampoos leave behind a constant residue of lipid, about 100 mg to 150 mg. Further shampooing for another few minutes does not reduce this residue appreciably. This oil is seemingly beyond the reach of surfactants......If our explanation is correct, the sequestration of sebum between cuticle cells is a biologically sound device to assure that there will always be a small amount of lipid to protect the fibre from environmental assaults, including highly efficient shampoos.†And then, this dynamic residue must take part of the “hair barrierâ€, a new and interesting concept.

All criticism is constructive, and I am open to new ideas.

Armando

(*) "Sebum secretion and sebaceous lipids." (Dermatologic Clinics, Vol. 1, No. 3, July 1983)