Study: Propecia Responders and Non-Responders

[Bryan]

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

The second study says:

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

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

No, Stephen, you don't understand what they said. Prior contact inhibition doesn't "change" the expression of those genes to "allow" an effect of TGF-Beta 1 in vitro. They merely said that contact inhibition AND TGF-Beta 1 both affect those same genes. That's completely different from the way you attempted to spin it.

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

" Expression of p45 reappeared 12 h after release from contact inhibition and 6-8 h after release from TGF-beta 1, while TGF-beta 1 prevented release from contact inhibition and maintained suppression of both p45 and cyclin D2. "

OF COURSE TGF-beta 1 "maintained suppression" of both p45 and cyclin D2, because THAT'S WHAT IT DOES, just like contact inhibition! :wink: You're trying to spin what they said into suggesting that contact inhibition somehow causes a permanent change in the response of the cells to androgens, just because of that possible common pathway. But they neither said nor implied any such thing! They merely said that if you keep supplying TGF-beta 1, then you will continue to have suppression of p45 and cyclin D2, even after the contact inhibition has stopped.

Do you understand now?

Bryan

 

[Bryan]

Based on `all' the available evidence, i don't think the in-vivo miniaturization of follicles, has anything to do with any action of DHT `within' the follicles....I know Bryan will make his usual excuses here, but if topical anti-androgens had any decent effect against male pattern baldness, the drug companies would have developed these commercially!

My goodness, you have a bit of a problem here, don't you? :wink: If you don't think that androgens have ANY direct effect at all on balding hair follicles, then how do you explain the fact that topical antiandrogens have at least SOME beneficial effect, even if they don't produce a full recovery of all lost hair?? You've got some explaining to do, Stephen...

Bryan

 

[S Foote.]

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

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

[quote="S Foote.":db0ad]I did make a mistake in debating this point, and that was assuming that you had some sense, so i didn't have to refer to the obvious. But i see i was wrong, so let me be `VERY' clear and consise now!

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

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

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

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

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

You mean BESIDES those cancer cells?

Bryan[/quote:db0ad]

Well Bryan i'am sorry to say that the authors of that study don't draw the same conclusions as you!

You have fallen into the trap of not reading the study properly, in your haste to try to put me down. You haven't even bothered to refer to `ALL' the tested cell types have you!

Rap yourself on the fingers with that ruler of yours Bryan

The study related to a number of prostate cell types, and this is the `AUTHORS' conclusion Bryan, quote:

" 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."


I rest my case!

S Foote.

 

[S Foote.]

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

The second study says:

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

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

No, Stephen, you don't understand what they said. Prior contact inhibition doesn't "change" the expression of those genes to "allow" an effect of TGF-Beta 1 in vitro. They merely said that contact inhibition AND TGF-Beta 1 both affect those same genes. That's completely different from the way you attempted to spin it.

[quote="S Foote.":87189]The study shows that TGF-Beta 1 `actually' prevents cell release `FROM' contact inhibition, so there is a `proven' precedent for what i am saying Bryan! Quote:

" Expression of p45 reappeared 12 h after release from contact inhibition and 6-8 h after release from TGF-beta 1, while TGF-beta 1 prevented release from contact inhibition and maintained suppression of both p45 and cyclin D2. "

OF COURSE TGF-beta 1 "maintained suppression" of both p45 and cyclin D2, because THAT'S WHAT IT DOES, just like contact inhibition! :wink: You're trying to spin what they said into suggesting that contact inhibition somehow causes a permanent change in the response of the cells to androgens, just because of that possible common pathway. But they neither said nor implied any such thing! They merely said that if you keep supplying TGF-beta 1, then you will continue to have suppression of p45 and cyclin D2, even after the contact inhibition has stopped.

Do you understand now?

Bryan[/quote:87189]

All i understand from you Bryan, is that you will do anything you can to avoid the real points!!

Of course there is not yet any proof of my speculation here, but it is a perfectly valid speculation based on the conclusions of the posted studies.

Contact inhibition and TGF-Beta 1 act via the same pathways, so i suggest a link, again as a `precedent'.

People can see beyond your personal `spin', and see the `possible' link for themselves Bryan!

So what have `YOU' got to offer us?

Normal terminal hair producing follicles, that are known `future' male pattern baldness follicles, are not switched to male pattern baldness `mode' by exposure to androgens.

So what is `YOUR' suggestion for the non-androgenic `switch' Bryan, if not contact inhibition? Let's hear `YOUR' explaination based on recognised `PRECEDENTS' in physiology? You have been avoiding this main issue throughout this debate!

I am suggesting a possible alternative explaination for the observations in male pattern baldness, based on precedents both in recognised physiology, and suggested by studies.

Let's hear your explainations using the `SAME' principles?

It's time to put up or shut up!!

S Foote.

 

[S Foote.]

Stephen, I said it badly.

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

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

I agree that not enough research into the `alledged' genetic `differences has been done yet.

I would like to see this done on `all' scalp follicles in young males pre-puberty. According to the current theory, those that are future male pattern baldness follicles, `should' have some genetic differences.

I would bet that they don't!

S Foote.

 

[Armando Jose]

Friends,
"I agree that not enough research into the `alledged' genetic `differences has been done yet.

I would like to see this done on `all' scalp follicles in young males pre-puberty. According to the current theory, those that are future male pattern baldness follicles, `should' have some genetic differences.

I would bet that they don't!

S Foote."

Bravo, I am with Stephen,..., if there is any genetic difference my own theory is completely dead.

To Bryan, Is sebum bad or good?
I don’t see you point of view. Necessary is not good in all cases. Imagine sebum as cholesterol. Cholesterol is necessary, but is it good?

And yes, my theory is based in type of blockage of sebum, but the inward blockage is the crucial in my opinion.

Armando

 

[mvpsoft]

Cholesterol is necessary, but is it good?

Of course it is good. Too much of any good thing is bad, however.

 

[Bryan]

Well Bryan i'am sorry to say that the authors of that study don't draw the same conclusions as you!

Oh really?? The only "conclusion" I drew is what they actually SAID: one specific type of prostate cancer cell went from being STIMULATED by androgens to being INHIBITED by androgens, after androgens were withheld from them for an extended period of time. That's the bottom-line, regardless of how you try to spin the results. It is indeed a "precedent" for a change in how cells respond to androgens, even it it's only in cancer cells.

Bryan

 

[Bryan]

All i understand from you Bryan, is that you will do anything you can to avoid the real points!!

Of course there is not yet any proof of my speculation here, but it is a perfectly valid speculation based on the conclusions of the posted studies.

Contact inhibition and TGF-Beta 1 act via the same pathways, so i suggest a link, again as a `precedent'.

You can "suggest" and "speculate" about anything you want, but the fact remains that there is not one iota of evidence that contact inhibition can flip-flop the way that cells respond to androgens. I want you to admit that, Stephen!

Normal terminal hair producing follicles, that are known `future' male pattern baldness follicles, are not switched to male pattern baldness `mode' by exposure to androgens.

No, not while sitting overnight in a petri dish. It may take YEARS for that to happen, not hours.

I am suggesting a possible alternative explaination for the observations in male pattern baldness, based on precedents both in recognised physiology, and suggested by studies.

There is NOTHING in any studies that suggests that contact inhibition causes cells to flip-flop in their response to androgens. That's your own peculiar spin. I know you'd give your left nut to find some real evidence for that, but there simply isn't any. If you are intellectually honest, you will admit that.

Bryan

 

[S Foote.]

All i understand from you Bryan, is that you will do anything you can to avoid the real points!!

Of course there is not yet any proof of my speculation here, but it is a perfectly valid speculation based on the conclusions of the posted studies.

Contact inhibition and TGF-Beta 1 act via the same pathways, so i suggest a link, again as a `precedent'.

You can "suggest" and "speculate" about anything you want, but the fact remains that there is not one iota of evidence that contact inhibition can flip-flop the way that cells respond to androgens. I want you to admit that, Stephen!

[quote="S Foote.":5074d]Normal terminal hair producing follicles, that are known `future' male pattern baldness follicles, are not switched to male pattern baldness `mode' by exposure to androgens.

No, not while sitting overnight in a petri dish. It may take YEARS for that to happen, not hours.

I am suggesting a possible alternative explaination for the observations in male pattern baldness, based on precedents both in recognised physiology, and suggested by studies.

There is NOTHING in any studies that suggests that contact inhibition causes cells to flip-flop in their response to androgens. That's your own peculiar spin. I know you'd give your left nut to find some real evidence for that, but there simply isn't any. If you are intellectually honest, you will admit that.

Bryan[/quote:5074d]

If `I'AM' intellectually honest! I don't know how you have the nerve Bryan?

Very simply, you say:

" You can "suggest" and "speculate" about anything you want, but the fact remains that there is not one iota of evidence that contact inhibition can flip-flop the way that cells respond to androgens. I want you to admit that, Stephen!"

Then you have the nerve to say, in respect of your contention that androgens can change the way cells respond `TO' androgens:

"No, not while sitting overnight in a petri dish. It may take YEARS for that to happen, not hours."

You dare to talk about me `suggesting' things without any evidence!

There is `FAR' more evidence for a central role of contact inhibition in changes in hair growth, than your pathetic guess work above. Apart from the study i quoted, you only have to read the hair loss forums! Read about the work of Fuchs, and the effects of B-Catenin, Wnt's etc on hair growth. Do some `REAL' research Bryan!

Again just show me `ONE' study that even remotely supports the notion, that prolonged exposure to androgens can change the way cells react `to' androgens, as you `guess' above?

Your persistence in trying to claim that prostate cancer cells `prove' what you claim, are just making you look foolish Bryan.

Prior to the cancer, androgens `CANNOT' create a `flip' to androgen resonse in prostate cells. It is the cancer that `ALLOWS' this change in androgen response as the authors of the study clearly state!

The `DIFFERENCE' in your argument is your claim that androgens `THEMSELVES', are creating the changes in cells that `THEN' allow a `flipped' response. You are claiming that androgens in the absense of any other factor, can change cells that `don't' flip, into cells that `do' flip!

So again for around the tenth time, show us `one' shred of evidence for the mechanism you propose????????????????????

You know you can't Bryan, and i just want you to admit that!

S Foote.





"

 

[S Foote.]

Friends,
"I agree that not enough research into the `alledged' genetic `differences has been done yet.

I would like to see this done on `all' scalp follicles in young males pre-puberty. According to the current theory, those that are future male pattern baldness follicles, `should' have some genetic differences.

I would bet that they don't!

S Foote."

Bravo, I am with Stephen,..., if there is any genetic difference my own theory is completely dead.

To Bryan, Is sebum bad or good?
I don’t see you point of view. Necessary is not good in all cases. Imagine sebum as cholesterol. Cholesterol is necessary, but is it good?

And yes, my theory is based in type of blockage of sebum, but the inward blockage is the crucial in my opinion.

Armando

Armando.

On a more constructive note, perhaps we should start another thread in this `experimental' forum about suggestions for future experiments?

I have a few ideas myself relating to this issue.

We can all argue points here, but we should really be trying to ecourage those in a position to do related experiments, to do these shouldn't we?

S Foote.

 

[Old Baldy]

Stephen and Armando: Even if you don't believe there are any genetic differences between a non-male pattern baldness follicle and a male pattern baldness follicle, there must be a genetic difference between those that have detrimental contact inhibition versus those that don't have detrimental contact inhibition. (If that's the cause of male pattern baldness.)

Either way, the ability to analyze genes will ultimately provide the answer. It will get to the root cause of male pattern baldness.

 

[Armando Jose]

Stephen;
I agree with you, it's important design experiments to probe any theory. What are your ideas?. But better in a new post.
Regarding my theory, North Korea could be a "good" experiment because actually is baned to wear long hair in men.

OlBaldy;
Certainly, analyze the DNA is very interesting. Cells in a "bad" situation express different genes than normal cells, but, could we find out the trigger of this "bad" situation?, I don't know.

Armando

 

[S Foote.]

Stephen and Armando: Even if you don't believe there are any genetic differences between a non-male pattern baldness follicle and a male pattern baldness follicle, there must be a genetic difference between those that have detrimental contact inhibition versus those that don't have detrimental contact inhibition. (If that's the cause of male pattern baldness.)

Either way, the ability to analyze genes will ultimately provide the answer. It will get to the root cause of male pattern baldness.

I don't think there is any difference in the way normal contact inhibition works in individuals. It is simply the normal switching off of cell multiplication when a certain level of `contact' pressure is experienced by the multiplying cells.

I am suggesting that in male pattern baldness, the higher pressure in the scalp of the individual, is increasing the resistence to follicle enlargement, so the `normal' cut off point in contact inhibition is reached earlier in the follicles enlargement. So i think it is a scalp `pressure' difference in individuals, and not any difference in the normal contact inhibition process itself.

It's like the follicle growth process is trying to blow up a balloon in the dermal tissue. The pressure `within' this `balloon' is in effect the normal contact inhibition `constant'. So the actual size reached by the follicle `balloon' is controlled by variations in the pressure in the dermal tissue around it. The higher this pressure resisting follicle enlargement, the earlier contact inhibition kicks in, the smaller the follicle.

According to the `Hydraulic' theory, the genetic differences primarily lie in the genes that ultimately control the levels of DHT, and the genes that ultimately determine our `plumbing' system characteristics. It is these factors that combine to determine the individuals scalp pressure.

Thanks for your interest Old Baldy and Armando.

I will post a new thread at the weekend about what i feel would be important experiments relating to male pattern baldness, i haven't got much time this week.

Regards.

S Foote.

 

[michael barry]

Great stuff S. Foote,

Im interested in your very well reasoned hydrolic theory. Im looking for ways to lower fluid volume in my top layers of scalp skin aslo.

Things you have noted: donutting of large grafts, the implasibility of "stetch back" claims concerning scalp reductions, body hair moved to the scalp growing long and thick like head hair, head hair moved to the body growing short and thin like body hair, the precept of fibrosis, the noted diuretic effects of spironolactone and minoxodil all have had a big effect on what Ive thought about male pattern baldness.

When people's eyebrows fall out, its considered a disease, but the follicles themselves are not blamed by the medical establishment. There is a word for this condition, but I forget it. Bill Clinton's mother had it. If our body hair began to fall out, Im sure it would be diagnosed as a skin disease. When our head hair falls out, science doesnt claim its a skin disorder, but claims hair is succeptible to a hormone that WE KNOW MAKES BODY HAIR GROW and starts postulating on "DNA clocks" in follicles and other ridiculous tripe. But body hair surgically moved to the head eventually grows just like head hair and vice versa. Obviously the skin around a follicle determines its growth then. A laser hair removal technichian told me "hair is hair" and we kill hair plug hair the same way we kill back hair and the back hair is actually harder to kill. Isnt it funny the "establishments" answer is expensive surgery that gets docs paid huge money, and an anti-DHT drug that one has to take for the rest of their lives, getting Merk paid huge money?
Is it not also REALLY funny that Upjohn still claims to not know why minoxodil grows hair??????? We know its not increased blood flow, many drugs can do that. Opening potassium channels and strengthening capillary cell walls might help, but in vertex area baldness would this account for minoxodils spledid performance in completely regrowing hair?

Im with you Stephen, there are too many people making money in baldness the way things are and this is why questions begging for more research seemingly are ignored. Now that the herbal people are weighing in on baldness, the picture is murkier than ever in the etiology of baldness understanding.

 

[S Foote.]

Hi Michael.

Thanks for your comments.

I think alot of the problems we have, are related to the vunerability we have as hair loss sufferers, and that someone somewhere is is always trying to `sell' us something!

I think these hair loss forums are very important, in that we can see peoples `real life' experiences of treatments, and ultimately sort out what is realistic and what is not!

Regards.

S Foote.

 

[irishlad87]

Hope i dont get in trouble for resurrecting this thread but im interested as it applies to my current situation. I recently got off finasteride after 3 years which im convinced i was a non responder and i started minoxidil 2weeks ago, just wondering have an members got off finasteride and went on minoxidil and had success.

 

[Swiss_Tampons]

Well. What can I say.

And yes, my theory is based in type of blockage of sebum, but the inward blockage is the crucial in my opinion.

Armando

Almost 12 years.

 

[irishlad87]

Well. What can I say.



Almost 12 years.

Whats your point man i dont get it as im a relative newbie. What dies it mean about sebum blockage because i used to be on accutane which suppresses sebum production.

 

[Swiss_Tampons]

Whats your point man i dont get it as im a relative newbie. What dies it mean about sebum blockage because i used to be on accutane which suppresses sebum production.

Ohh, sorry irish lad, it wasn't intended as an answer for you, it was only a sincere, spontaneous and thoughtless expression of my bewilderment! Some mumbo-jumbo really stick around perennially.

Howsoever, forget about sebum.