Study: Propecia Responders and Non-Responders

[Bryan]

Here's the sections of that Japanese study you think in some way support the `direct' theory.

>>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,<<

So what! The evidence you need to support the current theory is `missing' from this study as i think you know Bryan!

The reason I've cited that study and others like it is to demonstrate to you for the umpteenth time that androgens CAN directly affect hair follicles. You've tried to claim in the past that there's no way androgens can have such an effect. That claim is blatantly and palpably FALSE.

This study is essentialy the same as the Macaque study we discussed before. The `big' difference is that in the Macaque study, they `directly' exposed known `pre-balding' samples to androgens as well. As you know Bryan, direct exposure to androgens did `NOT' change healthy pre-balding follicle cells `INTO' balding follicle cells! http://endo.endojournals.org/cgi/content/full/138/1/356

The current `direct' theory says that androgens SHOULD directly `switch' these cells into balding mode. The Macaque study clearly `DISPROVES' this, and i'am willing to bet any similar human study would also show that this doesn't happen.

It doesn't happen overnight in a petri dish, Stephen. It takes YEARS for that to happen. All your rantings on that subject are for nothing, I'm afraid.

The in-vitro observations you are so fond of quoting in support of your arguments Bryan, are `AFTER' the fact. The samples you quote have `ALREADY' had their `particular' growth characteristics `CHANGED' by some kind of in-vivo process.

Well, I'll have to give you credit for at least acknowledging THAT, Stephen! Even if those growth characteristics are changed by something OTHER than exposure to androgens (let's face it, nobody knows for sure what causes it), you've made progress by admitting that they DO have different growth characteristics! :wink:

Further exposure to any number of substances in-vitro, including androgens, could just be magnifying the `particular' existing growth characteristics of the samples. Cream cheese could have the same effect as androgens on these `ALREADY' growth transformed cells. Do we then say male pattern baldness is `CAUSED' by cream cheese!! Thats the reasoning you are using here Bryan!

Let's not indulge in hypothetical "chicken-or-the-egg" speculations. The important point is that androgens DO directly affect hair follicles. Some of them for the better, some of them for the worse.

The all important cause of the `CHANGE' in hair growth characteristics is what we want to know about!! The studies show this is `NOT' done through direct exposure to androgens, so the `direct' theory is disproved, simple!

The "direct" theory is not disproved. We don't know exactly WHY hair follicles become sensitive to androgens, but we do know that they DO become sensitive to them.

You can't disprove a theory just by asking WHY something happens to be the case. For example, just because nobody can explain why the speed of light is the maximum speed limit in the universe, that doesn't disprove the Special Theory of Relativity! :wink:

All the observations in DHT related hair growth/loss, can be explained through `recognised' physiological mechanisms, by `ONE' primary action of DHT. This is an increase in the regular contractions of lymph vessels induced by DHT.

OH REALLY?? Stephen, please explain to us how DHT does that!

The only unresolved question this leaves is how my proposed influence of normal contact inhibition relates to the hair transplantation issue.

That's the Understament of the Year, so far! And I suspect that it will still be in that number 1 position at the end of the year 2005!

Bryan

 

[Bryan]

I suggest that DHT significantly increases lymphatic drainage efficiency, and that this is it's primary evolutionary function as a male hormone.

Explain how it does that. BE SPECIFIC.

I think that the `whole' miniaturization of follicles is an important point. We only have androgen receptors in the DP cells. So how come the `whole' follicle becomes miniaturized?

???

By an alteration in the production of diffusable growth factors (or inhibitors) from the DP cells, of course. Have you already forgotten the macaque study and the Japanese study and all the others that we've been discussing??

Bryan

 

[Old Baldy]

Stephen: What Bryan is saying about androgens having a direct affect on follicles is correct from all I've read. There's really no doubt about that. It's accepted science and sensible science from what's out there.

Now if your theory(s) add to solving different problems that occur as balding progresses that's great.

But, you shouldn't reject the fact that DHT has a direct affect on the health of the follicles. It does and it's not good.

 

[S Foote.]

Stephen: What Bryan is saying about androgens having a direct affect on follicles is correct from all I've read. There's really no doubt about that. It's accepted science and sensible science from what's out there.

Now if your theory(s) add to solving different problems that occur as balding progresses that's great.

But, you shouldn't reject the fact that DHT has a direct affect on the health of the follicles. It does and it's not good.

Hi Old Baldy.

I'am afraid the direct theory is just `NOT' sensible science, as Bryan would have you believe!

Bryan is applying double standards in the burden of proof issue in his last post above. I will respond to that later.

We can all argue our `personal' viewpoints, but whatever personal `spin' anyone tries to put on scientific issues, there is an established procedure for sorting what is valid from what is not!

What i would advise people to do is to read the established `rules' for scientific theories described here. http://phyun5.ucr.edu/~wudka/Physics7/N ... node5.html In particular the section on "Ockhams razor" which explains the requirements of a valid scientific theory.

The current `direct' theory of DHT in hair growth, gets `thrown out' by Ockams razor on a number of counts. This is because it requires `multiple' mechanisms to explain the relevant observations and experimental data. It also adds unnecessary complication.

But the most glaring fault in this theory is that to make it `fit', a mechanism of hormone/cell interaction has to be `invented', that goes against everything that is known about such interactions!

In science, it is the responsibility of the currently held theory to answer the questions according to the scientific rules. The current direct theory cannot do this, end of story!

The current theory is just bad science according to the established rules.

S Foote.

 

[S Foote.]

S Foote wrote:

So what! The evidence you need to support the current theory is `missing' from this study as i think you know Bryan!


>>The reason I've cited that study and others like it is to demonstrate to you for the umpteenth time that androgens CAN directly affect hair follicles. You've tried to claim in the past that there's no way androgens can have such an effect. That claim is blatantly and palpably FALSE.<<

Bryan, you know perfectly well that i have `NEVER' tried to claim that androgens cannot directly effect follicle cells in opposite ways `IN-VITRO', don't try to misrepresent what i have said!

But this does `NOT' happen without some kind of in-vivo `indirect' action of androgens `CHANGING' the way the samples `THEN' respond in-Vitro!!!!!!!

Any subsequent `CHANGED' reaction in-vitro, is not telling us what the all important mechanism of `CHANGE' is!!! To just `assume' that the change is a `delayed' direct effect of androgens via a `mystery' mechanism is just ridiculous!

The only thing the in-vitro tests actually `PROVE', is that the pre-existing growth characteristics of follicle cells, are `NOT' directly changed by exposure to androgens. The direct theory you support Bryan claims that they are. The `ACTUAL' experimental evidence dis-proves your theory, simple!



S Foote. wrote:
This study is essentialy the same as the Macaque study we discussed before. The `big' difference is that in the Macaque study, they `directly' exposed known `pre-balding' samples to androgens as well. As you know Bryan, direct exposure to androgens did `NOT' change healthy pre-balding follicle cells `INTO' balding follicle cells! http://endo.endojournals.org/cgi/content/full/138/1/356

The current `direct' theory says that androgens SHOULD directly `switch' these cells into balding mode. The Macaque study clearly `DISPROVES' this, and i'am willing to bet any similar human study would also show that this doesn't happen.


>>It doesn't happen overnight in a petri dish, Stephen. It takes YEARS for that to happen. All your rantings on that subject are for nothing, I'm afraid.<<

Where are the studies that confirm this `fantasy' speculation Bryan? You are the one who is `ranting' here! This claim of yours goes against everything that is known about hormone sensitive cells, so show us just a shread of `hard' evidence for this?

S Foote. wrote:
The in-vitro observations you are so fond of quoting in support of your arguments Bryan, are `AFTER' the fact. The samples you quote have `ALREADY' had their `particular' growth characteristics `CHANGED' by some kind of in-vivo process.


>>Well, I'll have to give you credit for at least acknowledging THAT, Stephen! Even if those growth characteristics are changed by something OTHER than exposure to androgens (let's face it, nobody knows for sure what causes it), you've made progress by admitting that they DO have different growth characteristics! <<

I'am begining to think that you don't even understand the theory you are trying to defend Bryan? You may make some `progress' by researching what your theory actually claims!


>>You can't disprove a theory just by asking WHY something happens to be the case. For example, just because nobody can explain why the speed of light is the maximum speed limit in the universe, that doesn't disprove the Special Theory of Relativity!<<

The speed of light is a `constant' Bryan, it doesn't `change'. The way follicle cells respond to androgens `changes'!! Your pretentious analogies really do `suck'.

Alright Bryan, lets talk about `REAL' science.

S Foote. wrote:
All the observations in DHT related hair growth/loss, can be explained through `recognised' physiological mechanisms, by `ONE' primary action of DHT. This is an increase in the regular contractions of lymph vessels induced by DHT.


>>OH REALLY?? Stephen, please explain to us how DHT does that!<<

By an already recognised effect of DHT on the neuromuscular system Bryan!

http://www.businesslafayette.com/dht.htm

No `magic' required!


S Foote. wrote:
I suggest that DHT significantly increases lymphatic drainage efficiency, and that this is it's primary evolutionary function as a male hormone.


>>Explain how it does that. BE SPECIFIC.<<

Your double standards are showing Bryan! You insist that i be specific in my explainations. But when i ask you to be specific in the evidence for your fantasy `genetic clock', you try to avoid the issue!

OK, i don't mind supporting my theory with `hard' evidence!

I propose that DHT increases lymphatic drainage by increasing the rate of the recognised regular contractions of these vessels described here. http://www.healthy.net/asp/templates/ar ... cle&ID=993 To do this, DHT must have some action upon the neuromuscular system to effect these contractions of muscle fibers in the vessel walls. Again, refer to this link http://www.businesslafayette.com/dht.htm

No `magic' required!

Point this out to Farrel will you, who asked this question on his censored site. I know he will not tell anyone on his site that i answered his point , but that speaks volumes for his faith in his own arguments!

S Foote. wrote:
I think that the `whole' miniaturization of follicles is an important point. We only have androgen receptors in the DP cells. So how come the `whole' follicle becomes miniaturized?


>>???

By an alteration in the production of diffusable growth factors (or inhibitors) from the DP cells, of course. Have you already forgotten the macaque study and the Japanese study and all the others that we've been discussing??<<

Even more guesswork Bryan! This is an `ASSUMPTION' made by these studies, it is `NOT' a proven fact!

The only mechanism widely accepted to effect the growth of all normal cell types in physiology, is contact inhibition!

No `magic' required.



S Foote. wrote:
The only unresolved question this leaves is how my proposed influence of normal contact inhibition relates to the hair transplantation issue.


>>That's the Understament of the Year, so far! And I suspect that it will still be in that number 1 position at the end of the year 2005!<<

Yet again Bryan when you can't mount a logical argument, you resort to sarcasm. You are not decieving people with this tactic, you just reduce your own credibility!

Tell us how the `direct' mechanism explains the immunology in male pattern baldness, and the major `opposite' changes in sweating efficiency with DHT induced hairgrowth/loss? Dont try to say these observations are not relevant to male pattern baldness, because they are, and any valid theory of male pattern baldness is required to explain them!

The Hydraulic mechanism can explain these observations by `ONE' mechanism. How many `multiple' mechanisms does the `direct' theory need?

All your psuedo scientific talk is just window dressing Bryan. You just can't explain the hard facts!

S Foote.

 

[Temples]

Sheesh. You guys give me a headache.

 

[Bryan]

But this does `NOT' happen without some kind of in-vivo `indirect' action of androgens `CHANGING' the way the samples `THEN' respond in-Vitro!!!!!!!

Any subsequent `CHANGED' reaction in-vitro, is not telling us what the all important mechanism of `CHANGE' is!!! To just `assume' that the change is a `delayed' direct effect of androgens via a `mystery' mechanism is just ridiculous!

Ok, suit yourself. From now on, I won't make any assumptions at all about what causes that change. Are you happy now, Stephen?

>>It doesn't happen overnight in a petri dish, Stephen. It takes YEARS for that to happen. All your rantings on that subject are for nothing, I'm afraid.<<

Where are the studies that confirm this `fantasy' speculation Bryan? You are the one who is `ranting' here! This claim of yours goes against everything that is known about hormone sensitive cells, so show us just a shread of `hard' evidence for this?

Ok, let's BOTH drop the issue of what causes those changes.

>>You can't disprove a theory just by asking WHY something happens to be the case. For example, just because nobody can explain why the speed of light is the maximum speed limit in the universe, that doesn't disprove the Special Theory of Relativity!<<

The speed of light is a `constant' Bryan, it doesn't `change'. The way follicle cells respond to androgens `changes'!! Your pretentious analogies really do `suck'.

Uh...the obvious point is that you can't disprove a theory just by continuing to ask why THIS, why THAT, why why why?? The analogy I presented above is an excellent one for you to ponder. I'm about to go to work on YOU (below) by asking similar "why why why" questions about your own theory! I hope you enjoy it!

S Foote. wrote:
All the observations in DHT related hair growth/loss, can be explained through `recognised' physiological mechanisms, by `ONE' primary action of DHT. This is an increase in the regular contractions of lymph vessels induced by DHT.

>>OH REALLY?? Stephen, please explain to us how DHT does that!<<

By an already recognised effect of DHT on the neuromuscular system Bryan!

http://www.businesslafayette.com/dht.htm

I read that article. So where in it is the evidence that DHT stimulates the regular contractions of lymph vessels?

S Foote. wrote:
I suggest that DHT significantly increases lymphatic drainage efficiency, and that this is it's primary evolutionary function as a male hormone.

>>Explain how it does that. BE SPECIFIC.<<

Your double standards are showing Bryan! You insist that i be specific in my explainations. But when i ask you to be specific in the evidence for your fantasy `genetic clock', you try to avoid the issue!

You're obviously focused on that one MINOR aspect, just because I don't have any hard evidence for what causes that change in hair follicles. You're milking that issue for all it's worth, aren't you?

I propose that DHT increases lymphatic drainage by increasing the rate of the recognised regular contractions of these vessels described here. http://www.healthy.net/asp/templates/ar ... cle&ID=993 To do this, DHT must have some action upon the neuromuscular system to effect these contractions of muscle fibers in the vessel walls. Again, refer to this link http://www.businesslafayette.com/dht.htm

Gosh, Stephen... You _propose_ that DHT does that. DHT _must_ have some action upon it. You're sounding awfully speculative, aren't you? I thought you were the man of science, the follower of Ockham's Razor? I thought you had all the loose ends in your theory neatly tied-up? :wink:

That second link is a nice general review article on the lymphatic system, but once again, where is the clear evidence that DHT has any effect at all on the movement of lymph? Sorry, but your "proposals" aren't good enough, just like my own assumptions about the early transition of hair follicles to being androgen sensitive weren't good enough for YOU (what's good for the goose is good for the gander). Get back to us when you have solid EVIDENCE that DHT does what you assume it does.

S Foote. wrote:
I think that the `whole' miniaturization of follicles is an important point. We only have androgen receptors in the DP cells. So how come the `whole' follicle becomes miniaturized?

>>???

By an alteration in the production of diffusable growth factors (or inhibitors) from the DP cells, of course. Have you already forgotten the macaque study and the Japanese study and all the others that we've been discussing??<<

Even more guesswork Bryan! This is an `ASSUMPTION' made by these studies, it is `NOT' a proven fact!

ROTFLAMAO!! How many more of these studies are going to be required before you actually BELIEVE them, Stephen? 10? 100? 1,000?

Bryan

 

[S Foote.]

Let me respond to the relevant points Bryan.


>Bryan said:
Ok, suit yourself. From now on, I won't make any assumptions at all about what causes that change. Are you happy now, Stephen?<

>S Foote said:
Where are the studies that confirm this `fantasy' speculation Bryan? You are the one who is `ranting' here! This claim of yours goes against everything that is known about hormone sensitive cells, so show us just a shread of `hard' evidence for this?<


>Bryan said
Ok, let's BOTH drop the issue of what causes those changes.<

You are quick to dismiss the issue of what causes the change in `direct' androgen sensitivity of follicle cells. But the fact that androgens do `not' cause this change, goes against what the supporters of the direct theory are saying about genetic pre-disposition! So this demonstrated lack of any androgen induced `change', dis-proves the current direct theory in the form it is being presented to us!!


>S Foote said:
The speed of light is a `constant' Bryan, it doesn't `change'. The way follicle cells respond to androgens `changes'!! Your pretentious analogies really do `suck'.<


>Bryan said:
Uh...the obvious point is that you can't disprove a theory just by continuing to ask why THIS, why THAT, why why why?? The analogy I presented above is an excellent one for you to ponder. I'm about to go to work on YOU (below) by asking similar "why why why" questions about your own theory! I hope you enjoy it!<<

But the `WHOLE' process of science, is about asking `WHY' and `HOW' Bryan!!

People cannot claim something just `happens' in a scientific theory, without explaining the `why's' and `how's'. Any valid scientific theory will explain the observations in a logical cause and effect way, by recognised and `logical' mechanisms in the relevant field, physics or biology for example.


>S Foote wrote:
I propose that DHT increases lymphatic drainage by increasing the rate of the recognised regular contractions of these vessels described here. http://www.healthy.net/asp/templates/ar ... cle&ID=993 To do this, DHT must have some action upon the neuromuscular system to effect these contractions of muscle fibers in the vessel walls. Again, refer to this link http://www.businesslafayette.com/dht.htm


>Bryan wrote:
Gosh, Stephen... You _propose_ that DHT does that. DHT _must_ have some action upon it. You're sounding awfully speculative, aren't you? I thought you were the man of science, the follower of Ockham's Razor? I thought you had all the loose ends in your theory neatly tied-up?

That second link is a nice general review article on the lymphatic system, but once again, where is the clear evidence that DHT has any effect at all on the movement of lymph? Sorry, but your "proposals" aren't good enough, just like my own assumptions about the early transition of hair follicles to being androgen sensitive weren't good enough for YOU (what's good for the goose is good for the gander). Get back to us when you have solid EVIDENCE that DHT does what you assume it does.<


There is a `BIG' difference in scientific terms between our two arguments here Bryan!

Both our `mechanisms' are speculative at this time. But my `speculation' about how DHT could increase lymphatic `pumping', is `possible' given accepted knowledge. If DHT `is' doing this, it has to be through the muscle system of the vessel walls, that already creates `KNOWN' periodic contractions of these vessels. DHT is already `KNOWN' to effect the neuromusculal system, so a `RECOGNISED' pathway exists for such an action of DHT on lymph vessels!!

There is also anecdotal evidence that men have more efficient lymphatic drainage than women, based on gender related conditions as i reference in my paper http://www.hairsite2.com/library/abst-167.htm This could logicaly be linked to the action of a sex hormone.

On the other hand, your proposal of a `genetic clock' controlling `when' follicle cells become `directly' sensitive to androgens, has `NO' possible precident in `KNOWN' physiology. In fact this goes `AGAINST' what we know about `directly' hormone sensitive cells!! More than that, your `mechanism' requires even more genetic `differences' in follicle cells, as `EACH' follicle is required to have a different `setting' for this `clock'!

This genetic clock proposal, is in the same vein as the `alien influence' example that Ockams razor warns against here. http://phyun5.ucr.edu/~wudka/Physics7/N ... 0000000000

This `genetic clock' conjecture, is additional `excess baggage' that cannot be tested, and is `NOT' required to explain the observations. This is the observation of a time `lapse' in follicle response to androgens. Existing `recognised' indirect physiology can already explain this!

>S Foote. wrote:
I think that the `whole' miniaturization of follicles is an important point. We only have androgen receptors in the DP cells. So how come the `whole' follicle becomes miniaturized?<


>Bryan wrote:
By an alteration in the production of diffusable growth factors (or inhibitors) from the DP cells, of course. Have you already forgotten the macaque study and the Japanese study and all the others that we've been discussing??<


>S Foote wrote:
Even more guesswork Bryan! This is an `ASSUMPTION' made by these studies, it is `NOT' a proven fact!<


>Bryan wrote:
ROTFLAMAO!! How many more of these studies are going to be required before you actually BELIEVE them, Stephen? 10? 100? 1,000?<


Just show me `ONE IN-VIVO' study that demonstrates `ALL' the `IN-VIVO' growth factor actions, that create `EQUAL' changes in `ALL' follicle cell types???

Again Bryan, the only `RECOGNISED' in-vivo mechanism that explains what we see `IN-VIVO', is contact inhibition!!

S Foote.

 

[Bryan]

>Bryan said
Ok, let's BOTH drop the issue of what causes those changes.<

You are quick to dismiss the issue of what causes the change in `direct' androgen sensitivity of follicle cells.

Not at all! I'm only JUST NOW dismissing it, after all this time! :wink: And I'm finally now dismissing it just to keep YOU from focusing on that one minor issue, and making hay out of it. I'm forcing you to face your worst nightmare, which is that there's solid evidence (maybe "proof' would be a better word to use here) that androgens affect hair follicles directly, no matter how painful it is for you to admit that!

Both our `mechanisms' are speculative at this time. But my `speculation' about how DHT could increase lymphatic `pumping', is `possible' given accepted knowledge. If DHT `is' doing this, it has to be through the muscle system of the vessel walls, that already creates `KNOWN' periodic contractions of these vessels. DHT is already `KNOWN' to effect the neuromusculal system, so a `RECOGNISED' pathway exists for such an action of DHT on lymph vessels!!

Maybe. Get back to me when you have solid physical evidence for that, in addition to simple theorizing.

On the other hand, your proposal of a `genetic clock' controlling `when' follicle cells become `directly' sensitive to androgens, has `NO' possible precident in `KNOWN' physiology.

Really? And is there a precedent for something like _contact inhibition_ causing a change in the way cells respond to specific hormones (androgens, in this case)? I believe I asked you that at least once before, and you ignored the question...

>Bryan wrote:
ROTFLAMAO!! How many more of these studies are going to be required before you actually BELIEVE them, Stephen? 10? 100? 1,000?<

Just show me `ONE IN-VIVO' study that demonstrates `ALL' the `IN-VIVO' growth factor actions, that create `EQUAL' changes in `ALL' follicle cell types???

I honestly don't understand what you mean by that, Stephen. As I've already explained to you, there are numerous studies now accumulating that show that hair follicle growth is affected by diffusable growth factors that come from the dermal papilla, in response to androgens. Some of them have even identified SPECIFIC growth factors, and one of those is that Japanese study which I cited. Now it's up to you to start BELIEVING those studies! I can lead you to water, but I can't make you drink! :wink:

Bryan

 

[Old Baldy]

Stephen: Bryan wrote:

I honestly don't understand what you mean by that, Stephen. As I've already explained to you, there are numerous studies now accumulating that show that hair follicle growth is affected by diffusable growth factors that come from the dermal papilla, in response to androgens. Some of them have even identified SPECIFIC growth factors, and one of those is that Japanese study which I cited.

Why is it you are rejecting the above quote? I'm failing to understand why you would not accept that this is what the medical community has pretty much concluded is happening with male pattern baldness.

This knowledge is "new" considering the time it takes to develop drugs (if they ever can be developed) that will "cure" a specific ailment. Just because a remedy hasn't been found yet doesn't mean the cause is being erroneously interpreted.

Don't you think medical researchers would have looked at the lymphatic system by now, or at least discovered that that is the pathway for the development of male pattern baldness? It seems to me that they have found the basic pathway and it isn't via the lymphatic system?

 

[S Foote.]

Bryan said
Ok, let's BOTH drop the issue of what causes those changes.<


S Foote said
You are quick to dismiss the issue of what causes the change in `direct' androgen sensitivity of follicle cells.

>Bryan said
Not at all! I'm only JUST NOW dismissing it, after all this time! And I'm finally now dismissing it just to keep YOU from focusing on that one minor issue, and making hay out of it. I'm forcing you to face your worst nightmare, which is that there's solid evidence (maybe "proof' would be a better word to use here) that androgens affect hair follicles directly, no matter how painful it is for you to admit that!<

You keep on trying to distract from the issue that disproves the direct theory, by calling it a `minor' detail! But this just doesn't wash Bryan. This is not about our personal opinions, it is about the scientific rules concerning theories.

To be valid a scientific theory puts `ALL' the relevant observations and experiments into context, to give a cause and effect pathway. The direct theory just cannot explain things according to these established `rules'.

OK, so androgens `directly' effect the growth rates of in-vitro samples in a way that seems to `mimic' the in-vivo male pattern baldness situation. So how does this `fit' with everything else? It doesn't fit at all with all the other relevant observations. Likewise, the current donor doninance interpretation cannot explain the observations in a way theories are supposed to!

In such a situation, we should re-evaluate the interpretations that have been made about `certain' experiments, and ask if there could be other explainations? Other explainations that `DO' fit the scientific rules!


>S Foote wrote
Both our `mechanisms' are speculative at this time. But my `speculation' about how DHT could increase lymphatic `pumping', is `possible' given accepted knowledge. If DHT `is' doing this, it has to be through the muscle system of the vessel walls, that already creates `KNOWN' periodic contractions of these vessels. DHT is already `KNOWN' to effect the neuromusculal system, so a `RECOGNISED' pathway exists for such an action of DHT on lymph vessels!!<


>Bryan wrote
Maybe. Get back to me when you have solid physical evidence for that, in addition to simple theorizing.<

It is theorizing based on accepted physiology!! I will ask you one more time Bryan, to provide us with at least `some' kind of recognised precident for your genetic `clock' hocus pocus!!


>S Foote wrote.
On the other hand, your proposal of a `genetic clock' controlling `when' follicle cells become `directly' sensitive to androgens, has `NO' possible precident in `KNOWN' physiology.<


>Bryan wrote.
Really? And is there a precedent for something like _contact inhibition_ causing a change in the way cells respond to specific hormones (androgens, in this case)? I believe I asked you that at least once before, and you ignored the question...<

I am sure i have answered this point before Bryan, but i have no objection to answering it again.

The precident you ask for Bryan, is `very' basic `recognised' multi-cellular physiology! Cells that have been growth restricted by contact inhibition, have had their growth response potential to `ANYTHING', `changed' at the very basic level. The `future' growth response in-vitro to anything, `INCLUDING' androgens, is going to be `different' to their growth response prior to modification by the contact inhibition process.

This is why it is so important to find the mechanism of `change'. The in-vito tests prove that androgens do `NOT' create this change!

>Bryan wrote:
ROTFLAMAO!! How many more of these studies are going to be required before you actually BELIEVE them, Stephen? 10? 100? 1,000?<


>S Foote wrote.
Just show me `ONE IN-VIVO' study that demonstrates `ALL' the `IN-VIVO' growth factor actions, that create `EQUAL' changes in `ALL' follicle cell types???<


>Bryan wrote.
I honestly don't understand what you mean by that, Stephen. As I've already explained to you, there are numerous studies now accumulating that show that hair follicle growth is affected by diffusable growth factors that come from the dermal papilla, in response to androgens. Some of them have even identified SPECIFIC growth factors, and one of those is that Japanese study which I cited. Now it's up to you to start BELIEVING those studies! I can lead you to water, but I can't make you drink!<<

But i `DO' believe those `in-vitro' studies Bryan, but they mean nothing in the in-vivo `REALITY' context!

In-vivo, the influence of contact inhibition is overuling. It doesn't matter what other cell signaling is going on, or the growth factor situation. Cell growth will be prevented!! In-vitro, contact inhibition doesn't happen until the cell growth hits the sides of the petrie dish!! Your favorite in-vitro studies just don't relate to the in-vivo `reality'!

One of the cell signaling systems known to be linked to contact inhibition, is WNT's. When Prof Fuchs experiments manipulated WNT's, it caused a major change in follicle size `in-vivo'. This is a clear precident for a `real' in-vivo role of contact inhibition in hair growth!!

Let me say this.

You and others, including some scientists still see the direct theory as
`correct'. That is your belief, and you are entitled to it.

I think it is seriously flawed as a scientific theory, and i believe the `real life' second rate performance of treatments based on it are bearing this out! You yourself are on the record as saying you can think of no rationale for the frontal loss often reported with dutasteride. That is no rationale according to the current theory Bryan!

If it was so simple as a direct action of androgens, the solution would also be simple! The drug companies would have developed topical anti-androgen treatments that would have `cured' us. At the very least, they could have used these as a preventitive treatment and made a fortune! This is where the direct theory has to make even more excuses for the poor performance of anti-androgens in male pattern baldness! Dont bother with these excuses Bryan, i've heard it all before!

As time goes on, i have no doubt that more and more scientists will also look for alternatives to the current direct theory, as some are now. This is from the response i got from Dr Sawaya.

"It is a very complex process, but your thoughts are very organized and on the right path, similar to what others have been proposing, and in some ways yours are more straightforward. I think you've done a good job in thinking this through."

So if the direct theory is correct, why are some professional hair loss scientists `ALSO' proposing similiar ideas as mine???

In an interview on this site, the leading transplant surgeon Dr Limmer stated that the original ideas about donor dominance might not be correct.
http://www.hairlosstalk.com/newsletter/article181.htm

As time goes by, the only people that will continue to cling to the current theory, will have some kind of vested interest in selling products based on it!

S Foote.

 

[S Foote.]

Stephen: Bryan wrote:

I honestly don't understand what you mean by that, Stephen. As I've already explained to you, there are numerous studies now accumulating that show that hair follicle growth is affected by diffusable growth factors that come from the dermal papilla, in response to androgens. Some of them have even identified SPECIFIC growth factors, and one of those is that Japanese study which I cited.

Why is it you are rejecting the above quote? I'm failing to understand why you would not accept that this is what the medical community has pretty much concluded is happening with male pattern baldness.

This knowledge is "new" considering the time it takes to develop drugs (if they ever can be developed) that will "cure" a specific ailment. Just because a remedy hasn't been found yet doesn't mean the cause is being erroneously interpreted.

Don't you think medical researchers would have looked at the lymphatic system by now, or at least discovered that that is the pathway for the development of male pattern baldness? It seems to me that they have found the basic pathway and it isn't via the lymphatic system?

I think that people reading this thread ought to be aware of something!

On Farrels site Old Baldy said in a now deleted thread:

"Guys, the hydraulic and sebum theories were around when I was a kid. They were considered wacko then as well as now. Twenty years later the sebum theory rose its ugly head again with Ferm-T. More quackery."

So you were quite clear about your opinion on my theory on Farrel's site!

But now you `appear' here as a `neutral' voice of reason, that `weighs' the arguments and just happens to decide in favour of Bryan!

What kind of sad double act is this!!

S Foote.

 

[Old Baldy]

I'm showing you respect because you geniunely believe in a form of the hydraulic theory. You use the lympathic system to get there. That wasn't the theory in my youth. In my youth they just said sebum was choking or blocking the hair follicle. Your theory is more thought out.

I also mentioned the vacum cleaner device where you put a bag over your head and attached it to your vacum cleaner. It was supposedly going to "clear" out the clogged follicles. A far cry from your theory where you feel the lymphatic system creates internal pressures that choke off the follicles. I assume you feel the lymphatic system creates this "pressure" out of its reaction to DHT?

Medical research doesn't point to that happening but your theory is a far cry from the quackery I heard as a kid. You can't even compare the two.

Your theory is far more technical and thought out than the "hydraulic" or "clogging" theories I heard as a kid.

I disagree with your theory only from reading about DHT and male pattern baldness as it is viewed currently by the medical community. Being a layman that's all I really have to go by. But don't compare your theory to the quackery types of hydraulic theories I heard when I was a child. They are simply not the same thing.

My main concern with your point of view is why you reject the mountainous amount of opinions from the medical community stating DHT has a direct effect on the hair follicles. Not a direct effect on some other system that then affects the hair follicles.

Bryan accepts those findings from the medical community, you don't.

 

[S Foote.]

I'm showing you respect because you geniunely believe in a form of the hydraulic theory. You use the lympathic system to get there. That wasn't the theory in my youth. In my youth they just said sebum was choking or blocking the hair follicle. Your theory is more thought out.

I also mentioned the vacum cleaner device where you put a bag over your head and attached it to your vacum cleaner. It was supposedly going to "clear" out the clogged follicles. A far cry from your theory where you feel the lymphatic system creates internal pressures that choke off the follicles. I assume you feel the lymphatic system creates this "pressure" out of its reaction to DHT?

Medical research doesn't point to that happening but your theory is a far cry from the quackery I heard as a kid. You can't even compare the two.

Your theory is far more technical and thought out than the "hydraulic" or "clogging" theories I heard as a kid.

I disagree with your theory only from reading about DHT and male pattern baldness as it is viewed currently by the medical community. Being a layman that's all I really have to go by. But don't compare your theory to the quackery types of hydraulic theories I heard when I was a child. They are simply not the same thing.

My main concern with your point of view is why you reject the mountainous amount of opinions from the medical community stating DHT has a direct effect on the hair follicles. Not a direct effect on some other system that then affects the hair follicles.

Bryan accepts those findings from the medical community, you don't.

OK Old Baldy, i'am sorry if i read you wrong, and i will answer your main point, which is a fair question.


You say:

"My main concern with your point of view is why you reject the mountainous amount of opinions from the medical community stating DHT has a direct effect on the hair follicles. Not a direct effect on some other system that then affects the hair follicles."

I think the big problem historicaly in hair loss research, is that key experiments have not been considered. in the context of a `complete' scientific theory. The danger of not considering `particular' experimental results in the context of a complete theory, is that assumptions can be made, about the `true' significance of certain experiments.

In this case it has been shown that androgens directly reduce the growth of male pattern baldness follicle cells in-vitro. So because we know male pattern baldness is related to androgens, it is easy to go Ah-Ah androgens are having a direct effect!

The same principle applies in the donor dominance issue. One type of transplantation seemed to show that follicles must be inherently `different' in the way they respond to androgens. So there again the conclusion was that androgens are creating male pattern baldness `directly'.

This `hypotheses' has been around for over 60 years, and is still the currently accepted `mechanism' as you know.

The problem in my opinion is that the direct action idea cannot logicaly explain any of the other observations in DHT related hair growth/ loss. Any sound theory `has' to do this according to the scientific rules! I have argued the points of contention as i see them in this and other threads.

If this was mainstream science, the interpretation of the initial experiments would be re-thought to see if there was another reason for the results, that made sense of the `whole' observations.

My `Hydraulic' theory was developed to try to explain `ALL' the relevant issues in DHT related hair growth/loss, in accordence with the rules of theories. The basic argument is here http://www.hairsite2.com/library/abst-167.htm

According to this, there are possible alternative explainations for what we see in both transplantation, and the in-vitro experiments.

If the cells in male pattern baldness follicles have been subject to normal `in-vivo' contact inhibition by an in-direct action of DHT, their `WHOLE' programed growth response has been altered! They are therefore likely to continue to demonstrate a growth restricted response in-vitro, to any number of substances. What the in-vitro experiments show `FOR SURE', is that androgens are not directly `CHANGING' the existing growth response of any of the samples. The direct theory, and the current donor dominance interpretation, says that androgens should directly change the growth response!

The point i would make to people is really this.

The direct theory has serious flaws for a number of reasons, and the range of experiments necessary to confirm `ANY' theory have just not been done yet in my opinion. Now that more and more professional hair loss researchers are questioning the assumptions of the existing theory, we might get these experiments done! Meanwhile, just don't take what `ANYONE' says on internet sites as `gospel' without reference to the recognised rules of science!

For reference, below is the letter i sent to experts for comments on my theory, that Dr Sawaya replied to.

S Foote.

______________________________________




Dear ---------

I would welcome your opinion on a factor that must, given accepted physiology, have the `final say' in the size of the in vivo anagen follicle. This factor is the basic mechanism in multi-cellular biology of contact inhibition.

My opinion on the role of contact inhibition in anagen follicle size, and the advantages of this in the evolution and function of hair, can be seen here http://www.hairsite2.com/library/abst-167.htm A slightly modified version of this paper was published in Medical Hypotheses (2002) 59 (5), 522-526. doi:10.1016/S0306-9877(02)00259-1, available on line at http://www.idealibrary.com


The basic reasoning goes like this.

The amount of hair produced is directly related to the period of anagen, and the size achived by the anagen follicle. In male pattern baldness, the anagen period is shortened, resulting in miniaturised follicles.

In multi-cellular biology, any organ `building' is subject to the ultimate control of normal contact inhibition. Contact inhibition ensures that organs can only be as large as the available space allows. This prevents biological structures from interfering with each other.

As the anagen follicle starts to enlarge, it has to push the surrounding dermal tissue aside. The greater the resistence to movement of the dermal tissue, the earlier normal contact inhibition will `kick in'. If the resistence is high, the anagen enlargement period will be turned off early by contact inhibition, resulting in miniaturised follicles. If the resistence is low, anagen enlargement can continue for longer, resulting in larger follicles and increased hair growth.

The only factor that could `modify' the resistence to movement of the dermal tissue, is the fluid pressure within it. If the fluid pressure is high, the tissue rigidity is increased, and therefore its resistence to movement. Likewise, if the fluid pressure is low, so is the resistence to movement.

This mechanism makes a link with high fluid pressure and reduced hair growth, and low fluid pressure and increased hair growth. In my opinion, hair follicles evolved to `read' the fluid pressure in surrounding tissue to adjust hair production in line with other temperature controls in evolving mammals. Please see "The hydraulic dermal model" section of my paper.

A role of contact inhibition mediated through hydraulic changes in male pattern baldness, does not conflict with in-vitro observations, or the donor dominance observed in transplanted grafts. Sample follicle cells `switched off' by contact inhibition, have been fundamentally altered compared to cells that continue to multiply. EG: samples from terminal hair producing follicles. Any different in-vitro response of such samples to androgens, or other substances is to be expected! The observed Hypoxia in follicle grafts demonstrates no `active' circulation within these grafts. No active circulation means no hydraulic changes! The grafts will remain in the `as transplanted state', demonstrating donor dominance.

In male pattern baldness we have hair loss, immune infiltrate and immune sensitivity, ultimate fibrosis, and tissue thickening. These are all recognised factors in edemous tissue. http://www.lymphoedema.org.au/lymphoed.htm

One way to increase hair growth according to this mechanism, is to increase the resistence of follicle cells to contact inhibition? The danger here is that these cells would then be far more likely to become tumorous. In my opinion, the results of Fuchs in manipulating the Wnt pathway, confirms a central role of contact inhibition in follicle developement. http://www.hhmi.org/fuchs/index.html

If you look at other cases of hair loss, the common factor in these conditions is an increase in tissue fluid pressure for one reason or another!

As far as HM like procedures are concerned, i think the implantation itself could create `one off' conditions? There is bound to be some kind of healing process here, and this could very likely allow increased cell multiplication initially, and the developement of a large anagen follicle. We know that an `over production' of cells can occour during the healing process, scar tissue for example?

This predicts a potential problem with follicles generated by HM? If these follicles cycle normally, come the next anagen phase, these would then also come under the influence of normal contact inhibition. If the scalp conditions have not changed, large HM generated follicles could only last for one cycle?

I would welcome your comments on this proposal.

Best Regards,

Stephen Foote.

 

[mvpsoft]

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?

 

[Bryan]

You keep on trying to distract from the issue that disproves the direct theory, by calling it a `minor' detail! But this just doesn't wash Bryan. This is not about our personal opinions, it is about the scientific rules concerning theories.

To be valid a scientific theory puts `ALL' the relevant observations and experiments into context, to give a cause and effect pathway. The direct theory just cannot explain things according to these established `rules'.

Oh bullshit, Stephen! You've concocted an eccentric theory and twisted it around and FORCED it to explain certain other phenomena, so now you're proudly trumpeting it as a Grand Unified Theory of Everything!

I can propose eccentric theories, too, and I can make them fit some of the other observed phenomena, just like you do. One of them goes something like this (I call it the "Leprechaun Theory" of hairloss!): Unbeknownst to any of us, microscopic little leprechauns inhabit our hair follicles. They just _love_ greasy, fatty foods, so they love to munch on all the sebum that comes out of the hair follicle canal! However, they're smart enough to know that fat isn't very good for them, so whenever they gorge on sebum, they be sure to gnaw on some extra fiber (the nearby hair shaft)! That's why when there's more DHT around that makes more sebum come out, the hair shaft also gets gnawed down to nothing!! And those damned leprechauns are rather uncouth: when they need to piss, they just let it go right down that canal for the pilosebaceous unit, where it eventually accumulates under the skin! That explains why there's what appears to be so damned much EDEMA in the skin where balding is taking place! :wink:

See what I mean, Stephen? Anybody can create eccentric theories and twist them into explaining things; but it's all ad hoc theorizing if you can't really explain ALL the facts. In your own case, you stumble when you try to explain donor dominance. You haven't yet found a credible way to account for that. Neither have you been able to explain the beneficial effect on balding from topical antiandrogens.

S Foote wrote.
On the other hand, your proposal of a `genetic clock' controlling `when' follicle cells become `directly' sensitive to androgens, has `NO' possible precident in `KNOWN' physiology.<

>Bryan wrote.
Really? And is there a precedent for something like _contact inhibition_ causing a change in the way cells respond to specific hormones (androgens, in this case)? I believe I asked you that at least once before, and you ignored the question...<

I am sure i have answered this point before Bryan, but i have no objection to answering it again.

The precident you ask for Bryan, is `very' basic `recognised' multi-cellular physiology! Cells that have been growth restricted by contact inhibition, have had their growth response potential to `ANYTHING', `changed' at the very basic level. The `future' growth response in-vitro to anything, `INCLUDING' androgens, is going to be `different' to their growth response prior to modification by the contact inhibition process.

???

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.

Bryan

 

[viperfish]

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???

 

[viperfish]

Stephen,
Would not cold beam laser theory somewhat be supported by what you are saying???

 

[Old Baldy]

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.

 

[S Foote.]

>S Foote wrote
You keep on trying to distract from the issue that disproves the direct theory, by calling it a `minor' detail! But this just doesn't wash Bryan. This is not about our personal opinions, it is about the scientific rules concerning theories.

To be valid a scientific theory puts `ALL' the relevant observations and experiments into context, to give a cause and effect pathway. The direct theory just cannot explain things according to these established `rules'.<


>Bryan wrote
Oh bullshit, Stephen! You've concocted an eccentric theory and twisted it around and FORCED it to explain certain other phenomena, so now you're proudly trumpeting it as a Grand Unified Theory of Everything!<

If that statement is what you really think Bryan, you have no understanding of what the scientific process is all about!

It's always the same tactic from you Bryan. This thread is not about my theory, it is about the current theory. I ask to to provide precidents for the mechanisms you believe support your opinions, but you can't do this so you try to distract from the issue by questioning my theory!

Then when i explain the plausibility of my theory using recognised physiology, you call it `eccentric'. Just shouting `eccentric' over and over again without any support, isn't going to convince people as you would like!


>Bryan wrote
I can propose eccentric theories, too, and I can make them fit some of the other observed phenomena, just like you do. One of them goes something like this (I call it the "Leprechaun Theory" of hairloss!): Unbeknownst to any of us, microscopic little leprechauns inhabit our hair follicles. They just _love_ greasy, fatty foods, so they love to munch on all the sebum that comes out of the hair follicle canal! However, they're smart enough to know that fat isn't very good for them, so whenever they gorge on sebum, they be sure to gnaw on some extra fiber (the nearby hair shaft)! That's why when there's more DHT around that makes more sebum come out, the hair shaft also gets gnawed down to nothing!! And those damned leprechauns are rather uncouth: when they need to piss, they just let it go right down that canal for the pilosebaceous unit, where it eventually accumulates under the skin! That explains why there's what appears to be so damned much EDEMA in the skin where balding is taking place! :wink:<

What is it you are just not getting about what is regarded in theories as acceptable, and what isn't??? I keep on trying to educate you by getting you to read about the scientific method described here. http://phyun5.ucr.edu/~wudka/Physics7/N ... node5.html For God's sake just read it will you!!

>>SNIP<< all your other bullshit Bryan!

Your `Leprechaun' theory get's slung out for exactly the `SAME' reason as the current direct theory. It `HAS' to rely on `MAGIC' mechanisms that have no `PRECIDENT' in accepted physiology! Having some precident is what makes the difference between what is a valid hypothesis in science, and what is not!

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. 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.

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

Again, this thread is `NOT' about my theory, it is about the validity of the current theory!

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!

But you know as well as i do that you can't quote `ANY' precedent for this!! Just continually trying to shout me down by calling me `eccentric', isn't fooling anyone! It is the current theory that is eccentric according to the recognised scientific process.

I have offered my opinions on the donor dominance issue, and an explaination in line with my theory based on research in HM. I am not going to lose any sleep over your opinion on this, when recognised experts like Dr Limmer even start questioning what `YOU' regard as `gospel', that speaks for itself!

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. If the direct theory was correct, this just wouldn't be so!!

You can try all you like to distract people from the points i am making here Bryan, but people here can see the realities for themselves.

It is very clear from the response i got from Dr Sawaya that professional scientists today are questioning the current theory as i am! So why don't you go and tell them they are being `eccentric'? Go on i dare you!

If you expect anyone to take your opinions seriously Bryan, just answer my question above without any more attempts at distracting from it!!!!

S Foote.