Study: Propecia Responders and Non-Responders

[S Foote.]

Bryan wrote:

Stephen, you haven't answered my question!! I didn't ask you to SPECULATE about what happens during contact inhibition, I asked you to cite for me some actual scientific evidence where such an alleged change in the reponse to androgens by contact inhibition actually was FOUND!! Can you do it, or is YOUR claim just as speculative as mine was (the "genetic clock" assumption)?? I eagerly await your response to this.

Stephen: Despite what you think, I don't automatically agree with everything Bryan says. (We had disagreements on how raw fats can reduce DHT levels in the scalp for example.) However, I did spend roughly 4 hours searching the internet for some proof that contact inhibition causes follicles to change their response to DHT. I couldn't find anything. I know 4 hours isn't that long but I didn't find anything. Nada!

I searched the internet for this possibility long before Bryan posed the question. I couldn't find anything from the medical community that adds creedence to that theory.

My failure to find anything along those lines is what caused me to question your theory in the first place. Bryan's lack of finding anything along those lines makes it two people that haven't found that to be true.

Stephen: If contact inhibition caused the follicles to react differently to DHT it would seem that that pathway would be known by now. How is that more difficult to discover than the direct effect theory?

It's like saying the spark from a spark plug doesn't directly cause the explosion in an internal combustion engine. Your argument would say the friction from the moving piston is what really fires the gas/air mixture. The spark from the spark plug is inconsequential. Which we all know isn't true.

The problem with experimenting with contact inhibition, is that it is an `in-vivo' action. In many ways it is easier to experiment `in-vitro' because of the reduced interactions. But then again, this is why in-vitro experiments cannot tell the whole story accurately!

At this time all the cell to cell signaling systems in contact inhibition have not been fully identified, so it's not easy to fully `prove' what i am proposing.

But i would argue that the work of Fuchs supports my proposed link with contact inhibition and in-vivo follicle size. http://www.hhmi.org/fuchs/index.html You can also see the relevance to factors known to be involved in contact inhibition, and the same factors discussed in relation to hair growth in these links. http://www.hair-forum.com/hairloss/Beta ... 31750.html http://www.google.com/search?q=beta+cat ... ISO-8859-1

Please remember that this thread is not about my theory, and don't allow Bryans distraction tactics to influence my points about the flaws in the current theory!

S Foote.

 

[S Foote.]

Stephen,

If your theory is correct, what implications do you feel it has for combatting hair loss? I mean, would it recommend, say, minoxidil over finasteride, or would it recommend some experimental treatment?

At this time i am not really happy with making specific recomendations.

I think it has been shown by peoples results that systematic drugs like finasteride/dutasteride are far more effective than topical 5ARI's, supporting a systematic action of DHT against a `direct' action. But then there are the sides to deal with.
I think minoxidil effects the same `Hydraulic' pathway because it shifts fluid away from the periferal tissues. http://www.hairsite4.com/dc/dcboard.php ... 051&page=2

I think anything that reduces fluid build up and inflamation in the scalp is going to be helpful.

S Foote.

 

[S Foote.]

Stephen,
What then do you suggest as a treatment??

Or are you suggesting people do not use some of the more proven treatments for hairloss in at least hope of slowing down the process???

No i think the current treatments that show `some' benefit, are reducing scalp fluid levels.

The problem is the side effects of systematic 5ARI's, and some of the other things people use. I think the increasing emphasis on the inflamation aspect is a move in the right direction. (edema and inflamation go hand in hand) http://www.lymphoedema.org.au/index.htm I also think that your reference to certain laser treatments is valid, as these have been developed to treat edema http://lymphatichealth.com/products1.htm http://www.annieappleseedproject.org/lastoredswel.html

The `trick' would be (according to the theory) to develope specific therapies to avoid/reduce scalp fluid build up, whilst avoiding systematic effects. But this would need some research.

S Foote.

 

[mvpsoft]

So if I'm understanding you correctly, you de-emphasize systemic approaches to inhibiting the formation of DHT such as propecia and dutasteride. Do you think these don't work, according to your theory, or do you think that your theory suggests better approaches that don't have side effects? I mean, dutasteride and finasteride clearly work in many people, so how do they reduce the buildup of fluid in the scalp?

What alternative research program would your theory suggest? Should we abandon the focus on DHT? I guess I don't understand your theory well enough to understand what role you think DHT plays. I think the direct theory's understanding of DHT is clear enough, but I don't understand your's. I also don't understand what treatment programs your theory suggests that aren't being pursued now.

 

[Bryan]

Old Baldy questions any proven link between cells effected by contact inhibition in-vivo, and a reduced growth response to androgens in-vitro. Well there is no `proven' link at this time, this is my `proposal' based upon `RECOGNISED' physiology.

Well, it's been like pulling teeth, but we've finally gotten you to admit what I've suspected all along: you have no evidence whatsoever that contact inhibition can cause cells to "flip-flop" in the way that they respond to androgens (I have no idea what you mean by "recognized physiology", since you obviously can't cite ANY example of such a thing occurring, whether it be by way of contact inhibition, or any other process).

Stephen, you went WAAAAAY out on a limb by hounding me about how I couldn't fully explain the "genetic clock" theory of how scalp hair follicles eventually become sensitive to androgens, and you even went so far as to claim that it disproves the "direct theory"; now that limb has broken off, and you've crashed to the ground below! :wink: You can't explain that transition in hair follicles any better than _I_ can. And now we all know it!

Of course specific experiments by those in a position to do these, would be required to test this one way or the other! This is the reason why when people enquire about possible treatments based on my theory, as people have here, i don't like to recommend anything specific at this time.

That's a strange non sequitur. What does that second sentence have to do with the first? What does the CAUSE of the flip-flopping have to do with what you would recommend as a treatment for balding?? I thought you believe that the follicles' sensitivity to androgens isn't relevant to balding??

At this time, my theory is just that, a theory! But it is valid as such because it uses recognised mechanisms that have `PRECIDENT'.

Excuse me, Stephen, but we now know that you do NOT have ANY recognized mechanism or precedent to explain the flip-flopping of hair follicle cells.

So just answer my question Bryan! You posted elsewhere that you could quote me a precident in accepted physiology, for cells to become hormone sensitive with exposure to that hormone over time. This `mechanism' is required by the current theory, so show us the necessary justification for this `speculation'? I have asked you to put your money where your mouth is on this question time and time again!

I didn't say I _could_ do that, I said I _may_ eventually be able to do that. So far, I don't have an example of that for you. Which means that we are both in the same boat on that particular issue: neither of us can explain the flip-flopping! :wink:

Please don't try to tell me how `effective' topical 5ARI's are! Everyone on hair loss forums can see that the systematic 5ARI's are far more effective than the topicals.

Really? Your theory is unable to account for the fact that topical RU58841 was more effective in stumptailed macaques than oral finasteride, or even the beneficial effects of other topical antiandrogens in humans, like fluridil and 11a-hydroxyprogesterone. It is also unable to account for donor dominance and the flip-flopping of hair follicle cells. You have a LOT of work to do on your theory, Stephen, before it's even remotely credible. Good luck to you.

Bryan

 

[Trent]

dammit... how do we get this RU product.

 

[S Foote.]

>Bryan wrote
Well, it's been like pulling teeth, but we've finally gotten you to admit what I've suspected all along: you have no evidence whatsoever that contact inhibition can cause cells to "flip-flop" in the way that they respond to androgens (I have no idea what you mean by "recognized physiology", since you obviously can't cite ANY example of such a thing occurring, whether it be by way of contact inhibition, or any other process).<<

Read on Bryan because you have a `BIG' humiliating suprise awaiting you!


>Bryan wrote
Stephen, you went WAAAAAY out on a limb by hounding me about how I couldn't fully explain the "genetic clock" theory of how scalp hair follicles eventually become sensitive to androgens, and you even went so far as to claim that it disproves the "direct theory"; now that limb has broken off, and you've crashed to the ground below! You can't explain that transition in hair follicles any better than _I_ can. And now we all know it!<

The only thing we `all' know now Bryan, is that you really `CANNOT' answer my simple question, and give some support to your `own' theory!


>S Foote. wrote:
At this time, my theory is just that, a theory! But it is valid as such because it uses recognised mechanisms that have `PRECIDENT'.<

>Bryan wrote
Excuse me, Stephen, but we now know that you do NOT have ANY recognized mechanism or precedent to explain the flip-flopping of hair follicle cells.<

Wait for it!!

>S Foote. wrote:
So just answer my question Bryan! You posted elsewhere that you could quote me a precident in accepted physiology, for cells to become hormone sensitive with exposure to that hormone over time. This `mechanism' is required by the current theory, so show us the necessary justification for this `speculation'? I have asked you to put your money where your mouth is on this question time and time again!<

>Bryan wrote
I didn't say I _could_ do that, I said I _may_ eventually be able to do that. So far, I don't have an example of that for you. Which means that we are both in the same boat on that particular issue: neither of us can explain the flip-flopping!<

So you `may eventually' be able to support your ideas in a proper scientific way Bryan? I don't know where you get the nerve to accuse me of being un-scientific! The theory you agree with has been around for over 60 years now, so how long do you need? 100, 200, 1000 years? I'am not suprised you are interested in this life extension thing. It's because you still want to be around in 100 years time on hair loss forums, to talk about stumptailed macaques isn't it!!

OK Bryan, let's get down to it. You said above:


"you have no evidence whatsoever that contact inhibition can cause cells to flip-flop" in the way that they respond to androgens (I have no idea what you mean by "recognized physiology", since you obviously can't cite ANY example of such a thing occurring, whether it be by way of contact inhibition, or any other process)"

Unlike you Bryan, i `CAN' quote a recognised `PRECIDENT' for the `flip flop' reaction to androgens induced by some other process, as proposed by my theory! Here is the link, read it and weep!

http://www.biochem.arizona.edu/miesfeld ... esfeld.pdf


This article reports on the `CHANGED' action of androgens on cell growth, when the gene transcriptional factors in the cells have been altered. By the way Bryan, contact inhibition `alters' gene transcriptional factors!!

This is one relevant section from the article. (Note that there are `several' examples of this!):

"There are several examples in which hormone activation of
the AR4 can actually lead to growth inhibition of prostate
cells. The PC-3 cell line is derived from a prostate carcinoma
and does not express AR (7, 8). Interestingly, ectopic expression
of AR cDNA can lead to slowed growth in these cells in
response to androgens (9 –11). Perhaps the most widely
used human prostate cell line is LNCaP, which expresses a
mutated AR that has reduced ligand discrimination (12–17).
LNCaP cells typically grow poorly in the absence of androgen
and are usually maintained in medium containing hormone
(18). However, propagation of these cells for an extended
period of time in hormone-free medium results in the
outgrowth of a variant cell line not dependent upon androgens
for enhanced proliferation. Interestingly, it was found
that androgen treatment of this LNCaP variant resulted in
decreased cell growth (19), suggesting that AR functions
were intact, although with an altered transcriptional response."

You can try to distract from this `recognised precident' for what i am saying all you like Bryan, but it is there for all to see!

This article `CLEARLY SHOWS' that changes in transcriptional factors, can `flip flop' the response of cells `TO' androgens!!

Now i have answered `every' damm question you have thrown at me in this thread! On the other hand you have consistently refused to even `TRY' to justify your opinions with `HARD' evidence. You rely instead on a diversionary retoric of `psuedo scientific' phrases!

The saying here in England Bryan is "put up or shut up".

People can see for themselves that you have no credibility at all when it comes to `true' science. But considering the way you always manage to avoid issues you can't explain, you could have a great future in politics!

S Foote.

 

[S Foote.]

So if I'm understanding you correctly, you de-emphasize systemic approaches to inhibiting the formation of DHT such as propecia and dutasteride. Do you think these don't work, according to your theory, or do you think that your theory suggests better approaches that don't have side effects? I mean, dutasteride and finasteride clearly work in many people, so how do they reduce the buildup of fluid in the scalp?

What alternative research program would your theory suggest? Should we abandon the focus on DHT? I guess I don't understand your theory well enough to understand what role you think DHT plays. I think the direct theory's understanding of DHT is clear enough, but I don't understand your's. I also don't understand what treatment programs your theory suggests that aren't being pursued now.

I think the systematic reduction of DHT has a place at this time, but i think this should be at the lowest dosage in the individual necessary to avoid adverse effects.

According to my theory, DHT is the most powerful, natural hair growth promoter there is! DHT `increases' hair growth over the vast majority of the body. I suggest it does this by generally reducing the tissue fluid pressures. The `opposite' effect on the scalp in some individuals, is down to a particular level of DHT creating opposite fluid dynamic effects in the scalp. Basicaly a `plumbing' system effect.

Reducing systematic levels of DHT will help to reduce the opposite effect, but once higher tissue fluid levels exist in the scalp, they are not easy to reverse. The edema creates a recognised immune sensitivity, and the situation tends to become self generating. This is a good info site on the effects of lymphedema http://www.lymphoedema.org.au/

So reducing systematic levels of DHT removes the `trigger', but the existing edema should also be addressed to get the most benefit.Thats where anti-inflamatory and anti-fibrotic topicals should help, as indicated in that link.

In the future, with the necessary research there could be a better way of doing things? If DHT is creating male pattern baldness via a `plumbing' problem, lets `fix' the plumbing!

It could be that a reletively minor surgery could make DHT irrelevant in male pattern baldness? This could potentialy be much less trauma than current hair transplant's, and be reversable if necessary!

It would be nice to have such a `one off' fix to the problem, but it would take some dedicated research!

Good luck.

S Foote.

 

[Old Baldy]

Stephen: I need you to explain how B-catenin effects male pattern baldness. If appears to fall under the "scalp health" area of curing male pattern baldness. You know reduce inflammation, etc.

 

[Bryan]

OK Bryan, let's get down to it. You said above:

"you have no evidence whatsoever that contact inhibition can cause cells to flip-flop" in the way that they respond to androgens (I have no idea what you mean by "recognized physiology", since you obviously can't cite ANY example of such a thing occurring, whether it be by way of contact inhibition, or any other process)"

Unlike you Bryan, i `CAN' quote a recognised `PRECIDENT' for the `flip flop' reaction to androgens induced by some other process, as proposed by my theory! Here is the link, read it and weep!
http://www.biochem.arizona.edu/miesfeld ... esfeld.pdf

Stephen! I'm laughing, not weeping!!

In your desperate attempt to find something (ANYTHING) that would save some face for you, you had to settle for something that happens in a certain specific type of PROSTATE CANCER CELL??? Didn't I clearly ask you for evidence in human scalp hair follicles, not cancer cells? :wink:

This article reports on the `CHANGED' action of androgens on cell growth, when the gene transcriptional factors in the cells have been altered. By the way Bryan, contact inhibition `alters' gene transcriptional factors!!

That's not good enough, Stephen! Your task was not just to prove that contact inhibition alters any old transcriptional factors at all (I don't deny the fact that it alters SOME transcriptional factors), your task was to prove specifically that it alters the RESPONSE TO ANDROGENS in hair follicles. And you still fail at that task! You've found no evidence, much less proof.

This is one relevant section from the article. (Note that there are `several' examples of this!):

No there isn't. There's only that one, having to do with LNCaP cells.

"There are several examples in which hormone activation of the AR4 can actually lead to growth inhibition of prostate cells. The PC-3 cell line is derived from a prostate carcinoma and does not express AR (7, 8 ). Interestingly, ectopic expression of AR cDNA can lead to slowed growth in these cells in response to androgens (9 –11). Perhaps the most widely used human prostate cell line is LNCaP, which expresses a mutated AR that has reduced ligand discrimination (12–17). LNCaP cells typically grow poorly in the absence of androgen and are usually maintained in medium containing hormone (18 ). However, propagation of these cells for an extended period of time in hormone-free medium results in the outgrowth of a variant cell line not dependent upon androgens for enhanced proliferation. Interestingly, it was found that androgen treatment of this LNCaP variant resulted in decreased cell growth (19), suggesting that AR functions were intact, although with an altered transcriptional response."

You can try to distract from this `recognised precident' for what i am saying all you like Bryan, but it is there for all to see!

This article `CLEARLY SHOWS' that changes in transcriptional factors, can `flip flop' the response of cells `TO' androgens!!

ROTFLMAO!! Stephen, I'm going to explain the two main reasons why this attempt of yours to explain hair follicle flip-flopping is an utter failure:

1) That's in PROSTATE CANCER CELLS with mutated genes (and a certain specific kind of cancer cell at that), not normal scalp hair follicles. You have utterly no evidence that such a thing as they describe would happen in hair follicle cells.

2) Probably the funniest thing that you're overlooking even in the case of those LNCaP cancer cells is that the change in the response to androgens isn't caused by an INDEPENDENT process like contact inhibition (which is what it's incumbent upon you to prove), it's caused by A CHANGE IN THE LEVEL OF ANDROGENS THEMSELVES!! They clearly explained that growing those cells for a long period of time with reduced (or increased, for that matter) levels of androgens is itself what causes the change in their subsequent RESPONSE to those same androgens! And hey, does that remind you of anything?? Sounds quite a bit like the "genetic switch" theory, doesn't it? :wink: That theory states that hair follicles gradually alter their response to androgens when they are exposed for several years to greatly increased levels of testosterone after puberty. To your chagrin, the study you cite above, if anything, actually supports the "genetic switch" theory, not YOUR theory!

Back to the drawing-board for you, Stephen.

Bryan

 

[S Foote.]

Stephen: I need you to explain how B-catenin effects male pattern baldness. If appears to fall under the "scalp health" area of curing male pattern baldness. You know reduce inflammation, etc.

B-Catenin is involved in cell-cell contact, and contact inhibition! PSI and Wnt's along with some other things often mentioned on hair loss sites, are also involved in contact inhibition.

I think that the manipulation of these substances can increase hair growth, by reducing the follicle cells response to normal contact inhibition. But this is inherently dangerous, because it can increase the risk of tumors. I would not personaly use anything that could interfere with `normal' contact inhibition.

Here are some related links.

http://www.jcb.org/cgi/content/full/146/4/855

http://www.virginia.edu/biology/develbi ... mbiner.htm

http://www.hair-forum.com/hairloss/Beta ... 31750.html

http://kinase.uhnres.utoronto.ca/Wnt_Rest/Bcat.html

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

S Foote.

 

[S Foote.]

Your response Bryan, was just as desperate as i thought it would be!!

I must say i am suprised at the lengths you will go to in order to try to preserve your fragile ego, even now deliberately distorting the facts!

You said

"That's not good enough, Stephen! Your task was not just to prove that contact inhibition alters any old transcriptional factors at all (I don't deny the fact that it alters SOME transcriptional factors), your task was to prove specifically that it alters the RESPONSE TO ANDROGENS in hair follicles."

" Didn't I clearly ask you for evidence in human scalp hair follicles, not cancer cells? "

You didn't ask me for any such thing Bryan! What you `ACTUALLY' said, as you well know is this.


"you have no evidence whatsoever that contact inhibition can cause cells to flip-flop" in the way that they respond to androgens (I have no idea what you mean by "recognized physiology", since you obviously can't cite ANY example of such a thing occurring, whether it be by way of contact inhibition, or any other process)"

I provided what you asked for! You have now suddenly changed your demands, and then you expect people to take you seriously in scientific debates?


>S Foote. wrote:
This is one relevant section from the article. (Note that there are `several' examples of this!):<

>Bryan wrote:
No there isn't. There's only that one, having to do with LNCaP cells.<

People can read for themselves Bryan, they don't need your distorted interpretations!

The `AUTHORS' of the study said:


"There are several examples in which hormone activation of the AR4 can actually lead to growth inhibition of prostate cells."

They then quoted this one example!! But obviously `YOU' must know better!

>Bryan wrote:
Probably the funniest thing that you're overlooking even in the case of those LNCaP cancer cells is that the change in the response to androgens isn't caused by an INDEPENDENT process like contact inhibition (which is what it's incumbent upon you to prove), it's caused by A CHANGE IN THE LEVEL OF ANDROGENS THEMSELVES!! They clearly explained that growing those cells for a long period of time with reduced (or increased, for that matter) levels of androgens is itself what causes the change in their subsequent RESPONSE to those same androgens!<

Absolute rubbish Bryan, the AUTHORS made no such connection as everyone can see, no matter how hard you squirm!!

It is quite clear that the `ACTUAL' transformation takes place in the total absense of androgens. So the transcriptional changes in gene function, CANNOT POSSIBLY be influenced by androgens for God's sake. Your sad attempt at `re-interpreting' the facts are just pathetic!

Your the one who claims that androgen responsive cells need to be `soaked' in androgens over time, to develope a growth restricting `flip'!! That article actually `DISPROVES' the very principle of your `magic' genetic clock Bryan!

Don't talk to me as if you are the `school teacher' here, and we all have to satisfy your demands! Don't talk crap like "Your task is this", or "It is incumbent on you"!!

I don't have to `PROVE' anything. It is the scientific responsibility of the currently accepted theory to `PROVE' things!!!

You have made it very clear to everyone in this debate that you can't `PROVE' a damm thing about your theory, or even provide any precident for it!!

All your egotistical ranting, and diversionary tactics isn't fooling anyone Bryan. I think you should look for another hobby!

S Foote.

 

[Bryan]

You said
"That's not good enough, Stephen! Your task was not just to prove that contact inhibition alters any old transcriptional factors at all (I don't deny the fact that it alters SOME transcriptional factors), your task was to prove specifically that it alters the RESPONSE TO ANDROGENS in hair follicles."

" Didn't I clearly ask you for evidence in human scalp hair follicles, not cancer cells? "

You didn't ask me for any such thing Bryan! What you `ACTUALLY' said, as you well know is this.

"you have no evidence whatsoever that contact inhibition can cause cells to flip-flop" in the way that they respond to androgens (I have no idea what you mean by "recognized physiology", since you obviously can't cite ANY example of such a thing occurring, whether it be by way of contact inhibition, or any other process)"

I provided what you asked for! You have now suddenly changed your demands, and then you expect people to take you seriously in scientific debates?

Stephen, what I said in that sentence above is accurate, with the exception of the last four words ("or any other process"): you STILL haven't presented any evidence that contact inhibition can cause cells (ANY kind of cells, for that matter, not just hair follicle cells) to flip-flop. Can't you even follow what I'm saying? Is this stuff too technical for you??

I will concede the one minor point about the cancer cells and the withholding of androgens, but that's of very little relevance to this issue, for obvious reasons.

>S Foote. wrote:
This is one relevant section from the article. (Note that there are `several' examples of this!):<

>Bryan wrote:
No there isn't. There's only that one, having to do with LNCaP cells.<

People can read for themselves Bryan, they don't need your distorted interpretations!

The `AUTHORS' of the study said:

"There are several examples in which hormone activation of the AR4 can actually lead to growth inhibition of prostate cells."

Yes, but we're not talking simply about whether androgens can inhibit the growth of prostate cells! The authors of that study clearly explained how certain prostate cancer cell lines can be either STIMULATED or INHIBITED, depending on the characteristics of that specific cell line, like whether it's differentiated or undifferentiated, etc. What WE are talking about is whether or not a cell can CHANGE the way that it responds to androgens. And the only example of that that they gave in that study is the LNCaP cell line.

I really think you need to carefully re-read that study. You don't seem to understand the fine-points of it.

>Bryan wrote:
Probably the funniest thing that you're overlooking even in the case of those LNCaP cancer cells is that the change in the response to androgens isn't caused by an INDEPENDENT process like contact inhibition (which is what it's incumbent upon you to prove), it's caused by A CHANGE IN THE LEVEL OF ANDROGENS THEMSELVES!! They clearly explained that growing those cells for a long period of time with reduced (or increased, for that matter) levels of androgens is itself what causes the change in their subsequent RESPONSE to those same androgens!<

Absolute rubbish Bryan, the AUTHORS made no such connection as everyone can see, no matter how hard you squirm!!

???

Excuse me?? They said in plain English that the change occurs when androgens are withheld from those cells for long periods of time. You _do_ read English, don't you, Stephen?

It is quite clear that the `ACTUAL' transformation takes place in the total absense of androgens. So the transcriptional changes in gene function, CANNOT POSSIBLY be influenced by androgens for God's sake.

LOL!!! It's influenced by the LACK of androgens! That's the point I'm trying to make to you! Being influenced either by androgens or the LACK of androgens are just flip-sides of the same coin!! Jesus Christ, Stephen!

Your the one who claims that androgen responsive cells need to be `soaked' in androgens over time, to develope a growth restricting `flip'!! That article actually `DISPROVES' the very principle of your `magic' genetic clock Bryan!

Nope, sorry...it gives another clear example of how exposure to androgens (or a LACK of exposure to androgens) can cause a change in the transcriptional response to androgens, just like the "genetic switch" theory hypothesizes. Deal with it, Stephen.

Ok, everybody...what have we learned in the last day or two? This is a clear, concise statement of what's been firmly established: Stephen has no evidence whatsoever (not to mention PROOF) that contact inhibition is capable of changing or altering the way that cells (ANY kind of cells, not to mention hair follicle cells) respond to androgens.

Don't talk to me as if you are the `school teacher' here, and we all have to satisfy your demands! Don't talk crap like "Your task is this", or "It is incumbent on you"!!

Hey, if you were right here in front of me, I'd whack your knuckles with a ruler every time you made a mistake! :lol:

Bryan

 

[S Foote.]

>S Foote. wrote:
Your the one who claims that androgen responsive cells need to be `soaked' in androgens over time, to develope a growth restricting `flip'!! That article actually `DISPROVES' the very principle of your `magic' genetic clock Bryan!<

>Bryan wrote
Nope, sorry...it gives another clear example of how exposure to androgens (or a LACK of exposure to androgens) can cause a change in the transcriptional response to androgens, just like the "genetic switch" theory hypothesizes. Deal with it, Stephen.

Ok, everybody...what have we learned in the last day or two? This is a clear, concise statement of what's been firmly established: Stephen has no evidence whatsoever (not to mention PROOF) that contact inhibition is capable of changing or altering the way that cells (ANY kind of cells, not to mention hair follicle cells) respond to androgens.<

It's been quite clear in the last few days, that `YOU' have learned nothing about the scientific process Bryan! Just trying like you have above to distort the reality here, isn't impressing anyone!

If you had bothered to read that study `properly', you would have seen that a number of androgen influenced prostate cells were studied.

This section of the authors summary tells the story! Quote:

"Discussion
Elucidating the effect that androgens have on prostate cell
growth is a critical issue for understanding the development
and maintenance of the prostate organ under normal conditions
and in prostate carcinoma. Most studies to date have
used human prostate cancer cell lines to study androgen
effects on cell growth; however, many of these models lack
expression of fully functional ARs. Our data presented here
using nontumorgenic CA25s cells provide evidence that normal
prostate cells behave differently than prostate cancer
cells with respect to androgen control of cell proliferation."

For the hard of thinking like you Bryan, this means that when cells have been `tranformed' in their integral growth characteristics by a factor capable of doing this, (in this case cancer), their growth response to androgens can be `flipped'.

The process of contact inhibition is `known' to create changes in the integral growth characteristics of cells. In fact, contact inhibition `must' influence the expression of the same genes involved in the developement of cancer! Because loss of the normal contact inhibition response in cells `IS' a tumorous transformation!

So i cite the examples in that study as a legitimate `PRECIDENT' for my proposal for the `flipped androgen response' in hair follicle cells, due to contact inhibition.

You asked me for a precident, i gave you one!! Your ego can't handle that, not my problem!

Nowhere, repeat `NOWHERE' in that study do the authors even `dare' to speculate, that the `core' growth change characteristics are `induced' by the presence or absense of androgens. They don't do that because the whole notion is ridiculous given accepted `PRECIDENTS', and the paper would not have been published!!!!!!!!

Even your desperate attempt to claim that the absense of androgens `dictates' the further evolution of this cell line, goes against known precidents!

The `norm' as most people reading posts on these forums know, is that androgen deprevation, triggers upregulation of receptors to try to maintain the `EXISTING' response to any available androgens!!

Are you proposing yet `ANOTHER' magic mechanism in the long list of these necessary for your theory to work?

If you are so convinced that contact inhibition plays no part in hair growth, how to you explain the effects of B-Catenin Wnt's etc, as reported on these forums?

I have provided credible precidents for my theory, but you then start demanding `proof'. I don't demand proof from you about your direct theory, just a simple `may be' precident. But you can't even do this for God's sake!


I'am afraid you have been found out in this debate Bryan!

<S Foote. wrote:
Don't talk to me as if you are the `school teacher' here, and we all have to satisfy your demands! Don't talk crap like "Your task is this", or "It is incumbent on you"!!<

>Bryan wrote
Hey, if you were right here in front of me, I'd whack your knuckles with a ruler every time you made a mistake!<

If i were stood in front of you Bryan, i don't think you would contemplate doing that? You may risk a problem removing your ruler from a place in your body where the sun don't shine! :wink:

S Foote.

 

[Bryan]

Oh, well... You've added nothing new in that last response, and I think we've taken this about as far as necessary. As I explained in my previous post, I suppose it's CONCEIVABLE that contact inhibition could cause hair follicles to "flip-flop" in their response to androgens, but you have no evidence whatsoever that it actually DOES IN FACT do that. That's the bottom-line. Your theory is still a house of cards, built on an extremely shaky foundation situated squarely over the San Andreas Fault!

Bryan

 

[S Foote.]

Oh, well... You've added nothing new in that last response, and I think we've taken this about as far as necessary. As I explained in my previous post, I suppose it's CONCEIVABLE that contact inhibition could cause hair follicles to "flip-flop" in their response to androgens, but you have no evidence whatsoever that it actually DOES IN FACT do that. That's the bottom-line. Your theory is still a house of cards, built on an extremely shaky foundation situated squarely over the San Andreas Fault!

Bryan

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!

The very fact that we are all still asking questions about male pattern baldness, 60 odd years after the `assumptions' of the current theory, should speak volumes to people about it's validity!

You like to throw into these debates phrases like " Your theory is still a house of cards, built on an extremely shaky foundation situated squarely over the San Andreas Fault! " But you cannot justify these statements in `true' scientific terms!

You also say:

"I suppose it's CONCEIVABLE that contact inhibition could cause hair follicles to "flip-flop" in their response to androgens, but you have no evidence whatsoever that it actually DOES IN FACT do that."

Well, neither you or anyone else has `proof' that a period of exposure to androgens, `converts' non responsive cells `to' responsive cells. You also have the distinct disadvantage of no known precidents for this, and recognised physiology `Actually' goes against this!

The only light at the end of the tunnel, is that more and more professional scientists, as well as people on these forums, are now questioning the assumptions of the current theory.

Hopefully, we might start to make some real progress?

S Foote.

 

[Bryan]

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.

The very fact that we are all still asking questions about male pattern baldness, 60 odd years after the `assumptions' of the current theory, should speak volumes to people about it's validity!

Not really. We're still asking questions about it because we're still learning all the biochemical intricacies. But I don't think that any serious scientist doubts the fundamental premises about the direct effect of androgens on hair follicle cells.

Well, neither you or anyone else has `proof' that a period of exposure to androgens, `converts' non responsive cells `to' responsive cells. You also have the distinct disadvantage of no known precidents for this, and recognised physiology `Actually' goes against this!

The LNCaP cells are such a "precedent", Stephen. How many times do we have to go over this?

The only light at the end of the tunnel, is that more and more professional scientists, as well as people on these forums, are now questioning the assumptions of the current theory.

I don't think so.

Bryan

 

[Old Baldy]

Did you guys ever think that both of your theories work in tandem to cause the follicles to "flip-flop"? Not mention old father time!!!

 

[Bryan]

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

Bryan

 

[HairlossTalk]

I absolutely love these threads. Stephen - stick around and initiate more such discussions like these with Bryan please! They're very interesting reading.

HairLossTalk.com