Study: Propecia Responders and Non-Responders

[S Foote.]

>>Old Baldy wrote
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".<<

I think you should consider the options here?

The `assumption' of the current theory is as you state above. But the evidence just does not support this notion of genetic `differences' in hair follicles! When follicle cell samples that are known to be `future' male pattern baldness follicles, are exposed to androgens in-vitro prior to the male pattern baldness effect, nothing happens! http://endo.endojournals.org/cgi/content/full/138/1/356 Androgens do `NOT' directly `change' normal follicles into male pattern baldness follicles. So there is no `different' genetic code `waiting' in these follicles, that is going to turn these into male pattern baldness follicles given `direct' exposure to androgens.

There are other explainations for an individuals risk of male pattern baldness for a certain level of DHT. In my opinion there are two factors involved here.

The first factor according to my theory, is of course the levels of DHT in the individual. This determines the induced restriction to fluid drainage from the scalp. The second factor is the individuals blood `feed' pressure to the scalp. If this is high, then the reduction in scalp fluid drainage created by DHT will create edema more easily and therefore male pattern baldness. If the feed pressure is lower, the same level of fluid drainage restriction, would be less significant, and scalp edema may not develope, ie no male pattern baldness.

In my opinion, this is what makes the difference in risk of male pattern baldness in individuals for the same level of DHT.

If this is what is happening, the higher blood feed pressure in individuals with male pattern baldness will also increase long term risk of heart problems. I understand that such a link has been made by published studies.

In regard to the evolutionary aspect.

I don't think that male pattern baldness evolved as a `cooling' mechanism. In the paper i refered too, Prof Cabanac suggested this `may' be a reason in evolution for the observed sweating changes. I think that male pattern baldness and the associated changes like the sweating factor, are secondary to a more important effect of DHT in evolution.

I think this is the same important reason for androgen driven characteristics in many primates, not just humans!

This is purely sexual `performance'!!

In most primate societies, it seems that everyone is `up for it' with everyone else! In such circumstances, the male that makes it stick to produce offspring, must have a `potency' advantage! Chimps have evolved large testicles that produce a lot of sperm to compete in this contest. I think the sexual behaviour of our nearest primate relatives, the Bonobo's tells the story! http://songweaver.com/info/bonobos.html

So what happens when people take systematic 5ARI's like finasteride/dutasteride? They have `less' sexual potency and ejaculate. So increased levels of DHT equal increased sexual competitiveness!

In the distant past when this was important to breeding success in our ancestors, higher levels of DHT would have evolved in `crowded' societies, compared to where smaller numbers of people occupied larger areas.

Is this why `original' native Americans have low levels of DHT, and little body hair or male pattern baldness? Low numbers in large spaces reduced the sexual competitiveness factor?

I don't think human hair patterns have any `direct' evolutionary significance. I think they are just the result of levels of DHT brought about for sexual reasons, and the complex blood `feed' that evolved to service the human brain!

S Foote.

 

[Old Baldy]

Great responses and food for thought. Very interesting.

What I mean by the initial trigger is the actual make-up of the hair follicle. For example, the hairs on the side of my head are immune to the balding process (in the main). The hairs on top of my scalp are not immune to the balding process (in the main).

I can only assume that the follicles on the side of the head do not have the same genetic (DNA type) of encoding that allows them to become susceptible to the balding process. In other words they never had the "trigger" in the first place.

Like I said in my firearms example. A gun without a trigger can never be fired in the first place. (Ok, add the sear to that example but you get what I mean.)

A firearm made with a trigger can be fired but if we put a lock on it we can prevent it from discharging the cartridge.

The "trigger" (in my examples) is the genetic code that allowed the follicle to become sensitive to the balding process. Many hairs on our head and bodies do not have that genetic code in the first place.

Am I explaining this well enough?

Bryan: It doesn't seem that cooling or sebum flow go deep enough to address that initial genetic encoding. I guess what I'm saying is that you can have all the sebum or heat in the world exposed to a "non-balding" follicle and it won't minaturize. That could be wrong but it doesn't appear to be wrong from what I've read.

Men with non-balding follicles on the top of their scalp produce sebum and need to cool their scalps but their follicles don't shrink. Why? Genetic structure? That's what I mean by the trigger. What is it in a shrinking follicle that allows it to become susceptible to ANY internal or external influence? What is it in a non-balding man's follicle that allows it to NOT become susceptible to any internal or external influence. Genetic make-up as encoded when created?

You guys brought up alot of info. to think about and digest. That will take time. I need to reread and think about things like this many times before they "sink" in. It takes me time to digest new stuff like this. Very interesting!!

Stephen: An example of how I need to reread things in order for them to sink in can be expressed from what you said about androgens.

Like Bryan stated, you did seem to go "full circle" in your argument when you indicated well those "were cancer cells". I need to reread your response a few times for your answer to sink in. Because, right now, it does appear that you went full circle?

Your theory on DHT and reproduction could be right but how does the sensitive follicle get created in the first place? To me, it must be an initial genetic encoding when created.

Oh, one last thing, Bryan - Your "tendency" statement is true from what I've read. But it would seem that you have to have that initial trigger in order for any degree of that tendency to express itself. In that way, in my mind, it is all or nothing.

Bryan wrote: "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."

I agree one hundred million percent. LOL!! And, if we can manipulate DNA encoding, we could reverse that evolutionary pressure?

 

[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!!

Ok whatever, Stephen. But YOU are the one who first brought up the cancer cells. If you don't think they're relevant enough for ME to use as evidence, then neither are they relevant enough for YOU to use as evidence, for the same reason (not that they ever even supported your theory in the first place).

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!

Neither is there any "precedent" for contact inhibition causing follicle cells to flip-flop in the way they respond to androgens. We're in the same boat, aren't we? :wink:

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!

Being "maintained" by TGF-beta 1 in-vitro?? What the hell is THAT supposed to mean?? You're not even making sense.

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:

Ahhh....but you see, Stephen, your theory does NOT explain the observations in male pattern baldness! :wink: I've explained that to you SOOO many times...

Bryan

 

[Bryan]

Re: To Old Baldy and Bryan

To Bryan:
“Sebum is good or bad?â€￾ Neither good nor bad, sebum is necessary for hair. You know, pilosebaceous system.

If sebum is NECESSARY for hair, then it must be GOOD for hair, right?? :wink:

"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 main factor by far is how much you touch your hair, play with it, comb it, etc. etc.

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 flowâ€￾ when this process is blocked anyway.

So WHAT is your theory of balding?? Are you saying that hairloss is caused by the "blockage" of sebum? I want to understand your theory, Armando, but you need to EXPLAIN it to me!

Bryan

 

[Bryan]

Bryan: It doesn't seem that cooling or sebum flow go deep enough to address that initial genetic encoding. I guess what I'm saying is that you can have all the sebum or heat in the world exposed to a "non-balding" follicle and it won't minaturize. That could be wrong but it doesn't appear to be wrong from what I've read.

Sebum and heat aren't really relevant in this context. Androgens are. If the "cooling theory" of hairloss actually is correct, then presumably natural selection favored the survival of individuals whose hair follicles happened to be altered in such a way that the ones on the scalp were being inhibited by androgens.

But it's just a GRADUAL influence. It will still vary considerably from one person to the next, and even from one follicle to the next. There are smooth gradations of responses: some follicles are strongly inhibited by androgens, some are mildly inhibited, some are not affected one way or the other, some are mildly stimulated, some are strongly stimulated. It's not an either-or situation.

Men with non-balding follicles on the top of their scalp produce sebum and need to cool their scalps but their follicles don't shrink. Why? Genetic structure? That's what I mean by the trigger. What is it in a shrinking follicle that allows it to become susceptible to ANY internal or external influence? What is it in a non-balding man's follicle that allows it to NOT become susceptible to any internal or external influence. Genetic make-up as encoded when created?

Again, we don't yet know the exact biochemical steps involved. Hopefully, some day we will. But that doesn't mean we can't speculate about the early evolutionary pressures which caused this condition, even if we don't yet know the exact chemistry behind it all.

Oh, one last thing, Bryan - Your "tendency" statement is true from what I've read. But it would seem that you have to have that initial trigger in order for any degree of that tendency to express itself. In that way, in my mind, it is all or nothing.

Maybe I'm still not sure what you mean by "initial trigger"!

Bryan

 

[Old Baldy]

That's ok Bryan. Maybe I'm out in leftfield as my starting point. Much like the guy who says soaps are acid.

In your post you indicate some follicles are not affected by DHT at all. Why? Is it because they don't have the genetic make-up to be affected by DHT in the first place. If so, those follicles don't have the ability (i.e., no genetic "trigger" or encoding) to ever be influenced by DHT. Is it a DNA type of encoding on the follicle that prevents DHT from triggering baldness in the first place?

That's what I'm calling the trigger. The follicle's genetic predisposition to be affected by DHT. Those without that genetic predisposition can be exposed to all the DHT in the world and won't go bald because they don't have the trigger. Maybe predisposition would be a better word than a slang term like trigger?

That predisposition is encoded in our follicles when created while in the womb is what I'm guessing. We are born with it in the first place is my guess. Could be wrong. Just a guess from all I've read.

Maybe you're thinking we're all encoded with the predisposition but to varying degrees. Could be. It's just as possible as my guess.

I don't think it is as possible because men with non-balding follicles still have DHT. Now do they have as much DHT as I do? Maybe not but I would imagine some even have more DHT than I do. Yet, they don't go bald. So you could be right but my GUESS is no. I wish I KNEW Da** it!!

Just thought of something Bryan. Let's say you're right and we're all born with the trigger (predisposition) to have our follicles influenced by DHT. I still think getting rid of that predisposition by genetic manipulation is the secret to curing baldness. More so than continuously applying or ingesting medicines that neutralize the effect of DHT on our follicles.

Is this "Star Trek" or "pie-in-the-sky" type of thinking? Forty years ago I would say yes, today no.

 

[Bryan]

In your post you indicate some follicles are not affected by DHT at all. Why? Is it because they don't have the genetic make-up to be affected by DHT in the first place. If so, those follicles don't have the ability (i.e., no genetic "trigger" or encoding) to ever be influenced by DHT. Is it a DNA type of encoding on the follicle that prevents DHT from triggering baldness in the first place?

That's what I'm calling the trigger. The follicle's genetic predisposition to be affected by DHT. Those without that genetic predisposition can be exposed to all the DHT in the world and won't go bald because they don't have the trigger. Maybe predisposition would be a better word than a slang term like trigger?

But here's what I don't like about the word "trigger": it strongly implies an either/or situation. It makes you think of a gun that's either fired or not fired! :wink: But there IS no either/or situation here. There is a smooth gradation of responses, as I mentioned before. I'm sure you could find individuals whose scalp hair follicles are only mildly adversely affected by androgens, so they don't present with noticeable balding under ordinary circumstances; yet if you give them large amounts of exogenous androgens, they _will_ start to bald.

I'm not prepared at the moment to speculate on the exact biochemical mechanism(s) behind that smooth gradation of responses to androgens.

I don't think it is as possible because men with non-balding follicles still have DHT. Now do they have as much DHT as I do? Maybe not but I would imagine some even have more DHT than I do. Yet, they don't go bald. So you could be right but my GUESS is no. I wish I KNEW Da** it!!

I think there's much more variation in the RESPONSE that various hair follicles around the body have to androgens than there is variation in simple LEVELS of androgens. For example, think of a beard hair follicle that's situated just inches away from a miniaturizing frontal scalp hair follicle! Those two RESPOND in a totally different and opposite way! :wink: See my point?? It's not just that the beard follicle lacks a balding "trigger", it's actually STIMULATED by androgens!!

Just thought of something Bryan. Let's say you're right and we're all born with the trigger (predisposition) to have our follicles influenced by DHT. I still think getting rid of that predisposition by genetic manipulation is the secret to curing baldness. More so than continuously applying or ingesting medicines that neutralize the effect of DHT on our follicles.

Sure, but it'll be quite a while before we know enough to be able to attack the problem that way.

Bryan

 

[Old Baldy]

Yes, that makes sense Bryan. There IS alot of variation in how a follicle reacts to androgens around the body. Follicles behave in opposite ways depending on where they are located and what type of follicle they are.

Yes, maybe it is the gradation that has to be looked at and "tweaked". Yes, that could be as much an answer to the secret. Just control that gradation.

When will they discover how to control the response to DHT in your opinion?

 

[S Foote.]

>>Old Baldy wrote
Stephen: An example of how I need to reread things in order for them to sink in can be expressed from what you said about androgens.

Like Bryan stated, you did seem to go "full circle" in your argument when you indicated well those "were cancer cells". I need to reread your response a few times for your answer to sink in. Because, right now, it does appear that you went full circle?<<

I'am sorry, i can see how i may not have made my self clear on this point, so i will try to do that now.

The LNCaP cells i quote are prostate cells, that have been altered at the genetic level by cancer. Before these cells became cancerous, androgens cannot create a `negative' effect on their growth by either their presense or absense. Only `AFTER' they are effected by cancer, do the cells `THEN' have the ability to `evolve' a growth restriction in the absense of androgens.

This `change' in the cellular response to androgens, is `NOT' created `BY' androgens, it is created by the cancer process.

Bryan would have us believe that androgens can `directly' induce this kind of change in hair follicle cells. He is trying to claim that androgens in `themselves' can change the way that cells respond `TO' androgens. But he cannot provide us with any precedents, or any other other sort of justification for this `mechanism'.

It is quite clear from the quoted study, that it is genetic changes induced by a factor `other' than androgens, (the cancer), that `flip' the androgen response in cells. It is not androgens that create the change to androgen response as Bryan is trying to claim!


>>Old Baldy wrote
Your theory on DHT and reproduction could be right but how does the sensitive follicle get created in the first place? To me, it must be an initial genetic encoding when created.<<

But if the follicles `are' initialy geneticaly different, why are androgens making no difference to their existing growth rates in-vitro?

Again, this `assumption' of geneticaly different follicles, is just something that is `needed' by the current theory! It is certainly not needed to explain androgen related changes in hair growth!

Just because androgens can show a growth restricting action on `already' balding follicle cells in-vitro, people jump to conclusions about the `actual' in-vivo effect? I have tried in this debate to point out why this is a dangerous assumption, that is `NOT' supported by the hard evidence.

As i see it, the assumptions made by one interpretation of the transplantation issue years ago, was the bigest mistake ever made in hair loss research. Ever since then, every experiment has been interpreted in a way designed to try to `fit' this basic assumption. The trouble is, further experiments have not fitted with the current donor dominance interpretation.

People should ask themselves why the scientific method demands that a valid theory `must' explain `ALL' the relevant observations? http://phyun5.ucr.edu/~wudka/Physics7/N ... node5.html

This is simply because `assumptions' can be made about what individual observations or experiments mean! If the conclusions of individual experiments can't be made to fit the whole thing, the conclusions have to be re-thought!

This is long overdue in hair loss research!

S Foote.

 

[Old Baldy]

I see now Stephen. Makes sense.

Bryan admits that genetic manipulation is a good way to go but it is long into the future. His last statement in response to my thread said that.

His way would work and the "answers" seem to be coming in faster for solving the problem his way than our way.

 

[S Foote.]

S Foote. wrote:
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
Ok whatever, Stephen. But YOU are the one who first brought up the cancer cells. If you don't think they're relevant enough for ME to use as evidence, then neither are they relevant enough for YOU to use as evidence, for the same reason (not that they ever even supported your theory in the first place).<<

See my post to Old Baldy.

S Foote wrote
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!

>>Bryan wrote
Being "maintained" by TGF-beta 1 in-vitro?? What the hell is THAT supposed to mean?? You're not even making sense.<<

Well it is all explained by those studies Bryan. If you can't grasp that, there is no point trying to talk science with you!

S Foote. wrote:
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!!

>>Bryan wrote
Ahhh....but you see, Stephen, your theory does NOT explain the observations in male pattern baldness! I've explained that to you SOOO many times...<<

Thats just one of your regular vague responses Bryan, designed to try to convince an internet audience that you have replied to my points SOOO many times before.

This kind of window dressing doesn't impress people Bryan! You have had more than one opportunity in this debate to explain to people `WHY' my theory doesn't explain the observations, so let's hear it? What are you so afraid of?

People can see that i have answered every point you have made, whilst you can't answer `any' of my questions!

S Foote.

 

[S Foote.]

I see now Stephen. Makes sense.

Bryan admits that genetic manipulation is a good way to go but it is long into the future. His last statement in response to my thread said that.

His way would work and the "answers" seem to be coming in faster for solving the problem his way than our way.

But genetic manipulation is `NOT' the way to go according to the latest research, and this is a very important point!!

If contact inhibition `is' the controlling factor in in-vivo follicle size, it would be very dangerous to `mess' with the genes involved!

Normal contact inhibition is a `safety' that prevents cells from multiplying where the is no `space' for this. If we manipulate genes to overcome contact inhibition, we produce tumorous cells!

The work of the leading researcher Professor Fuchs shows that if we mess with pathways known to be involved in contact inhibition, we can significantly increase hair growth. But the `nasty' down side is increased risk of tumors! http://www.hhmi.org/fuchs/index.html

If you search the hair loss forums for info into the latest hair multiplication research, there is also reference to increased risk of tumors!

How much more evidence do we need for a central role of contact inhibition in in-vivo hair growth???

The way to go is to provide more `space' for the natural enlargement of anagen follicles.

S Foote.

 

[Bryan]

>>Like Bryan stated, you did seem to go "full circle" in your argument when you indicated well those "were cancer cells". I need to reread your response a few times for your answer to sink in. Because, right now, it does appear that you went full circle?<<

I'am sorry, i can see how i may not have made my self clear on this point, so i will try to do that now.

{SNIP the rest of your tap-dancing around the issue}

You dodged Old Baldy's point: YOU are the one who first brought up the cancer cells in an attempt to bolster your theory, then a short while later you backed away from it, saying "they're only CANCER cells". You can't have it both ways, Stephen! :wink:

Bryan

 

[Bryan]

>>Bryan wrote
Ok whatever, Stephen. But YOU are the one who first brought up the cancer cells. If you don't think they're relevant enough for ME to use as evidence, then neither are they relevant enough for YOU to use as evidence, for the same reason (not that they ever even supported your theory in the first place).<<

See my post to Old Baldy.

I did. See my reply to your post to Old Baldy.

>>Bryan wrote
Being "maintained" by TGF-beta 1 in-vitro?? What the hell is THAT supposed to mean?? You're not even making sense.<<

Well it is all explained by those studies Bryan. If you can't grasp that, there is no point trying to talk science with you!

No it isn't explained by those studies. Explain to us how you think they indicate that contact inhibition causes the subsequent negative reaction to androgens in vitro. You're BLUFFING again, Stephen. You think that you can get away with just some very general technical statements, and that we won't notice that they don't really say anything one way or the other about your theory. You are sadly mistaken about that.

Bryan

 

[Old Baldy]

Stephen wrote:

But genetic manipulation is `NOT' the way to go according to the latest research, and this is a very important point!!

If contact inhibition `is' the controlling factor in in-vivo follicle size, it would be very dangerous to `mess' with the genes involved!

Normal contact inhibition is a `safety' that prevents cells from multiplying where the is no `space' for this. If we manipulate genes to overcome contact inhibition, we produce tumorous cells!

The work of the leading researcher Professor Fuchs shows that if we mess with pathways known to be involved in contact inhibition, we can significantly increase hair growth. But the `nasty' down side is increased risk of tumors!

I'm not saying manipulate genes to combat hydraulic factors, if they exist in a detrimental way. I'm saying manipulate genes to overcome the influence of DHT only in specific areas of the body. Might be pie-in-the sky but that's all I'm saying. I mean, how do you manipulate genes only in specific areas of the body?!

If scientists are ever able to do this, and it didn't cure male pattern baldness, then they could go after other possible causes.

I understand that under the contact inhibition theory you wouldn't want to manipulate the gene to overcome internal pressures. It would be like a "bursting balloon" (i.e., cause abnormal growth).

 

[S Foote.]

>>Like Bryan stated, you did seem to go "full circle" in your argument when you indicated well those "were cancer cells". I need to reread your response a few times for your answer to sink in. Because, right now, it does appear that you went full circle?<<

I'am sorry, i can see how i may not have made my self clear on this point, so i will try to do that now.

{SNIP the rest of your tap-dancing around the issue}

You dodged Old Baldy's point: YOU are the one who first brought up the cancer cells in an attempt to bolster your theory, then a short while later you backed away from it, saying "they're only CANCER cells". You can't have it both ways, Stephen! :wink:

Bryan

I think your the `Fred Astair' around here Bryan :wink:

Now you are just deliberately misquoting me Bryan. Show me where i said "they're only CANCER cells". ? That isn't what i said at all and you know it!!

I did make a mistake in debating this point, and that was assuming that you had some sense, so i didn't have to refer to the obvious. But i see i was wrong, so let me be `VERY' clear and consise now!

`BEFORE' these prostate cells `BECAME' cancerous, they were `NOT' capable of a restricted growth, induced either by the presence or absense of androgens. `AFTER' the cancer process has `CHANGED' these cells, androgens can `THEN' have a `DIFFERENT' effect!

It's very simple Bryan! This does provide a precedent for what i have said here, whether you agree or not!

On the other hand YOU admit you can provide no precedent WHATSOEVER, for exposure to androgens to `CHANGE' the way cells respond `TO' androgens.

As a supporter of the currently accepted theory, the burden of proof is `YOURS'. So where's your `proof' Bryan??

S Foote.

 

[S Foote.]

>>Bryan wrote
Ok whatever, Stephen. But YOU are the one who first brought up the cancer cells. If you don't think they're relevant enough for ME to use as evidence, then neither are they relevant enough for YOU to use as evidence, for the same reason (not that they ever even supported your theory in the first place).<<

See my post to Old Baldy.

I did. See my reply to your post to Old Baldy.

[quote="S Foote.":22181]>>Bryan wrote
Being "maintained" by TGF-beta 1 in-vitro?? What the hell is THAT supposed to mean?? You're not even making sense.<<

Well it is all explained by those studies Bryan. If you can't grasp that, there is no point trying to talk science with you!

No it isn't explained by those studies. Explain to us how you think they indicate that contact inhibition causes the subsequent negative reaction to androgens in vitro. You're BLUFFING again, Stephen. You think that you can get away with just some very general technical statements, and that we won't notice that they don't really say anything one way or the other about your theory. You are sadly mistaken about that.

Bryan[/quote:22181]

There is no `technical bluff' here Bryan, if you don't understand this you shouldn't get involved in scientific debates!

The second study says:

"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 if contact inhibition and TGF-Beta 1 are `using' the same genes, prior contact inhibition in-vivo can change the expression of these genes to then allow an effect of TGF- Beta 1 in-vitro.

The study shows that TGF-Beta 1 `actually' prevents cell release `FROM' contact inhibition, so there is a `proven' precedent for what i am saying Bryan! Quote:

" 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. "



Now do you get it?

S Foote.

 

[S Foote.]

Stephen wrote:

But genetic manipulation is `NOT' the way to go according to the latest research, and this is a very important point!!

If contact inhibition `is' the controlling factor in in-vivo follicle size, it would be very dangerous to `mess' with the genes involved!

Normal contact inhibition is a `safety' that prevents cells from multiplying where the is no `space' for this. If we manipulate genes to overcome contact inhibition, we produce tumorous cells!

The work of the leading researcher Professor Fuchs shows that if we mess with pathways known to be involved in contact inhibition, we can significantly increase hair growth. But the `nasty' down side is increased risk of tumors!

I'm not saying manipulate genes to combat hydraulic factors, if they exist in a detrimental way. I'm saying manipulate genes to overcome the influence of DHT only in specific areas of the body. Might be pie-in-the sky but that's all I'm saying. I mean, how do you manipulate genes only in specific areas of the body?!

If scientists are ever able to do this, and it didn't cure male pattern baldness, then they could go after other possible causes.

I understand that under the contact inhibition theory you wouldn't want to manipulate the gene to overcome internal pressures. It would be like a "bursting balloon" (i.e., cause abnormal growth).

You say:

"I'm saying manipulate genes to overcome the influence of DHT only in specific areas of the body"

Based on `all' the available evidence, i don't think the in-vivo miniaturization of follicles, has anything to do with any action of DHT `within' the follicles. I think as i have said before, that it is a more systematic action of DHT that leads to early contact inhibition of anagen growth in-vivo.

So it's hard to see how a local genetic manipulation `(if this would even be possible as you say), would effect the situation? If such a thing is going to effect the systematic production of DHT, we may as well take dutasteride! If the blocking of the androgen receptors is the goal, then i cant see how a local effect in the scalp (if possible), is going to help?

Remember. if it was just a case of blocking the androgen effect in male pattern baldness follicles as the current theory suggests, why are there no really effective topical anti-androgens that work in humans? So why would such a blocking action by genetic manipulation fair any better?

I know Bryan will make his usual excuses here, but if topical anti-androgens had any decent effect against male pattern baldness, the drug companies would have developed these commercially!

I don't think any genetic manipulation is going to be safe `and' effective, and the only kind that has `proven' to be effective changes the parameters of contact inhibition. Which is a dangerous thing to do!

S Foote.

 

[Bryan]

Now you are just deliberately misquoting me Bryan. Show me where i said "they're only CANCER cells". ? That isn't what i said at all and you know it!!

Ok, you're right. I shouldn't have put quote marks around that, as if those were your exact words. However, that's the GIST of what you said.

I did make a mistake in debating this point, and that was assuming that you had some sense, so i didn't have to refer to the obvious. But i see i was wrong, so let me be `VERY' clear and consise now!

`BEFORE' these prostate cells `BECAME' cancerous, they were `NOT' capable of a restricted growth, induced either by the presence or absense of androgens.

HUH??? You don't know very much about the prostate, do you, Stephen? You better do some research about the inhibitory effects of antiandrogens and 5a-reductase inhibitors on the normal, non-cancerous prostate! :wink:

`AFTER' the cancer process has `CHANGED' these cells, androgens can `THEN' have a `DIFFERENT' effect!

No, you need to re-read that abstract until you understand what they said. The cancer cells went from being STIMULATED by androgens to being INHIBITED by androgens, WHILE THEY WERE CANCEROUS. It happens when androgens are withheld from them for extended periods of time.

It's very simple Bryan! This does provide a precedent for what i have said here, whether you agree or not! On the other hand YOU admit you can provide no precedent WHATSOEVER, for exposure to androgens to `CHANGE' the way cells respond `TO' androgens.

You mean BESIDES those cancer cells?

Bryan

 

[Old Baldy]

Stephen, I said it badly.

What I see possible with gene therapy could involve analyzing hair follicles of non-balding men and compare their genetic make-up with those hair follicles of balding men.

Once a definite "pattern" or difference is noted, the genes could be manipulated to combat male pattern baldness. (Whatever it is that is causing male pattern baldness.)