BRyaN: more q's about ARs

[jimmystanley]

So then if Fluridil worked really well and you were a good responder then there would be no need to take finasteride right?

If A & B then C....the logic is simple and high quality. A sounds like it is true too.

 

[Bryan]

guys can have super high DHT levels but never go bald since they do not have follicle cells that have those wacky androgen receptors. sorry Chewey

ALL HUMAN SCALP HAIR FOLLICLES CONTAIN ANDROGEN RECEPTORS!

I want to clarify any possible confusion over something I've talked about in the past: I've said that the evidence shows that on average, balding guys do tend to have more androgenic activity than non-balding guys, but in my opinion, most of the problem probably comes from balding guys having a greater SENSITIVITY to androgens. I think there's some misunderstanding over what that word "sensitivity" means (or at least, what _I_ mean when I use that word).

Consider two very different types of human hair follicles: a beard follicle, and a frontal scalp hair follicle from a balding person. They have several of the same characteristics, including the following: They both have plenty of 5a-reductase. They both have lots of androgen receptors. They both have steroid sulfatase enzymes (which cleave inactive sulfated steroids into their active components), and other enzymes which help convert weaker androgens into more potent androgens.

And yet those two different hair follicles have totally different RESPONSES to androgens! Androgens make beard follicles nice and big and healthy, but they make frontal scalp follicles...well, you already know what they do to scalp follicles! :-x When I talk about different "sensitivities" to androgens that different guys have, I'm not really referring to different numbers of androgen receptors or different amounts of 5a-reductase, I'm mainly referring to those different types of RESPONSES to androgens. See what I mean?? For example, someone who has high levels of DHT and yet still has a flourishing full head of hair is a person whose genetics are such that androgens don't have nearly as much of a negative influence on the growth of his scalp hair as they do in the rest of us poor saps who are balding. The various growth factors in his scalp hair follicles (TGF beta-1, VEGF, IGF-1, HGF, etc.) aren't altered as much by androgens as they are in the rest of us.

This is the bottom-line that I want people to understand: part of the balding problem, at least, may indeed have to do with somewhat increased levels of androgenic activity in those of us afflicted with this condition; but I feel that most of the problem has to do with an altered RESPONSE to androgens in our scalp hair follicle cells, a response that's tilted more in the direction of growth inhibition than it is in normal individuals.

Bryan

 

[Old Baldy]

Thanks for the clarification Bryan.

Jimmy: I was confused on the sequence of events that occur when T enters the DP. I can see by your subsequent posts that you didn't have that confusion. I wasn't saying UR is non-existant.

I thought the androgen sensitive genes allowed the androgen receptors to react to T in a bad way. It's just the opposite. The androgen receptors react to T first and that starts the bad cascade of events. That's where I was confused. I had the cart before the horse so to speak. Nothing to do with UR. Sorry for not understanding how you thought either.

I thought the androgen sensitive genes produced more androgen receptors. That is apparently TOTALLY wrong. So, even if more androgen receptors are produced (in the DP) because of finasteride., finasteride. still negates their ability to produce androgen sensitive genes. (You know, like Bryan said, finasteride. might stop AR's in our balding scalps from starting the "bad" cascade of events in the first place.) So maybe UR, as I thought of it, isn't really that "dangerous"?

I had it COMPLETELY the opposite. I thought androgen sensitive genes started the bad cascade of events when exposed to T and allowed the AR's to flourish and do more damage. It's the AR's that start this insidious process. I thought it was androgen sensitive genes. Wrong!! (And, from all I've read, I should have known this sequence by now - DUH!!)

Bryan clarifying the sensitivity subject helped alot. I definitely had the cart before the horse. I understand the sequence of events better now.

Da** this male pattern baldness confuses me sometimes!! (I mean what the heck did I think ANDROGEN RECEPTORS could have meant except that they are ANDROGEN RECEPTORS for Godsakes. Sometimes I embarass myself.)

 

[Bryan]

I thought the androgen sensitive genes produced more androgen receptors. That is apparently TOTALLY wrong. So, even if more androgen receptors are produced (in the DP) because of finasteride., finasteride. still negates their ability to produce androgen sensitive genes. So maybe UR, as I thought of it, isn't really that "dangerous"?

That paragraph is rather confusing to me. I've read through it several times in an effort to understand it, but without total success! Let's be clear about the following issues:

1) A gene is essentially a sort of "blueprint" or "schematic" inside the cell's nucleus which specifies the structure of specific proteins. The cell uses those "blueprints" to actually construct those proteins, which then become a dizzying array of substances: some of them are used as structural materials for the cell, some of them are hormones which then diffuse out of the cell and travel through the blood to other locations in the body, some of them are enzymes that are used within the cell (the 5a-reductase enzyme is a perfect example of that!), and some of them are RECEPTORS for various hormones (like the androgen receptor!).

2) I would call any gene "androgen sensitive" if its expression is changed in some way (either increased or decreased), in response to androgenic stimulation. Some genes are not altered at all by androgens.

3) Androgen receptors are proteins that are produced in the cell, just like many other proteins. There is a specific gene which codes for that particular protein.

4) The gene ITSELF which produces androgen receptor protein appears to be "androgen sensitive", because when you reduce the production of DHT inside the cell, it apparently causes the cell to activate that gene to produce more androgen receptors, as part of a feedback mechanism. In other words, it's probably the way the cell tries to maintain androgenic homeostasis.

5) People need to stop worrying about that androgen receptor upregulation, because if you stifle the activity of androgens enough with antiandrogens and/or or 5a-reductase inhibitors, then it won't matter HOW many damned androgen receptors the cell makes in a compensatory effort.

Bryan

 

[Old Baldy]

Well, now da**it Bryan, maybe I wasn't wrong. I'm so confused now I'm going to have to go back and read ALL those gene articles I read when first starting out researching male pattern baldness.

Bryan, you wrote:
"4) The gene ITSELF which produces androgen receptor protein appears to be "androgen sensitive", because when you reduce the production of DHT inside the cell, it apparently causes the cell to activate that gene to produce more androgen receptors, as part of a feedback mechanism. In other words, it's probably the way the cell tries to maintain androgenic homeostasis."

So I was right in my initial opinion on the sequence of events.

If the genes produce more AR's to counter the effect of finasteride., for example, why do you say that there can't be enough additional AR's produced to defeat finasteride.? Is it because the AR's themselves cannot start the bad sequence of events? It must be due to the lack of the required enzyme that allows the production of DHT?

Forget all I said before indicating I put the cart before the horse. I apparently hadn't.

I'm EXTREMELY confused right now as to why more AR's cannot ultimately defeat ANY dosage of anti-androgen? I mean, some of the Type I & II still survive?

(This may be the most confused I've been since I started researching male pattern baldness. I need an aspirin!)

 

[Old Baldy]

Well Bryan: I guess I'll just have to accept what you said in (5) of your most recent post above. If there's "little" or "nothing" for the AR's to "work with" than I guess there could be a guzzillion of them and it wouldn't matter.

Do you still really like Dr. Sawaya? That woman has me going in CIRCLES!! :lol:

 

[Bryan]

If the genes produce more AR's to counter the effect of finasteride., for example, why do you say that there can't be enough additional AR's produced to defeat finasteride.? Is it because the AR's themselves cannot start the bad sequence of events?

Of course not. The androgen receptor can't stimulate the process of gene transcription/translation all by itself. An androgen has to bind to the receptor first, then the WHOLE COMPLEX (the androgen/androgen-receptor complex) gets translocated to the nucleus of the cell, where it then binds with DNA and starts all the dirty work.

It must be due to the lack of the required enzyme that allows the production of DHT?

Right. An androgen has to bind with the receptor, first. No 5a-reductase, no DHT (although I personally think other androgens can do the dirty work, too, although to a lesser extent).

I'm EXTREMELY confused right now as to why more AR's cannot ultimately defeat ANY dosage of anti-androgen? I mean, some of the Type I & II still survive?

Well, if you reduce the number of available androgen molecules enough, what harm could they do, if there's only a very very few?? The sharply reduced number of androgen molecules becomes the bottle-neck there that can't fully be compensated for just by increasing the number of receptors.

Bryan

 

[Bryan]

Well Bryan: I guess I'll just have to accept what you said in (5) of your most recent post above. If there's "little" or "nothing" for the AR's to "work with" than I guess there could be a guzzillion of them and it wouldn't matter.

Exactly!

Do you still really like Dr. Sawaya? That woman has me going in CIRCLES!! :lol:

Let's put it this way: my feelings about Dr. Sawaya are very very mixed nowadays! :wink:

Bryan

 

[Old Baldy]

Thank you Bryan. I took two aspirins!! They got rid of my headache!

Man, did I go full circle.

 

[chewbaca]

up

 

[jason566]

So if you say have an increase in facial hair growth after 4 months on finasteride and your hair frontal hair has gotten thinner does that mean you could be having a negative reaction to the finasteride due to the increase in free test?

 

[jimmystanley]

bryan...

1. you talk about sensitive cells that cause male pattern baldness as being the ones with 'negative effects' on hair growth factors. Is this the part of male pattern baldness that we know nothing about, or could you give us a further explanation on why there are negative effects instead of positive ones (subjective positive) (or point us to where we can learn more)

2. Also, if there are lots of different cells have androgen receptors, aside from the ones that cause male pattern baldness, is it possible that using an anti androgen may cause some damage to the cell? IN other words, if these cells claim to demand androgens then is it harmful in anyway to deprive them of androgens (other than it will stop the whole male pattern baldness process)?

3. thanks a lot for giving us retards a helping hand in figuring this stuff out :hairy:

 

[jimmystanley]

gotta bump it

 

[Bryan]

bryan...

1. you talk about sensitive cells that cause male pattern baldness as being the ones with 'negative effects' on hair growth factors. Is this the part of male pattern baldness that we know nothing about, or could you give us a further explanation on why there are negative effects instead of positive ones (subjective positive) (or point us to where we can learn more)

Yep, that's the part of male pattern baldness that we know nothing about. Nobody yet understands the "paradoxical" effect of androgens on hair follicles (why they stimulate growth in most body hair follicles, but suppress growth in most scalp hair follicles). Scientists are working on that puzzle as we speak.

2. Also, if there are lots of different cells have androgen receptors, aside from the ones that cause male pattern baldness, is it possible that using an anti androgen may cause some damage to the cell? IN other words, if these cells claim to demand androgens then is it harmful in anyway to deprive them of androgens (other than it will stop the whole male pattern baldness process)?

Well, keep in mind that men who are castrated can go on to live lengthy lives, although all the effects of having drastically reduced androgen levels are still in a certain amount of doubt (James Hamilton wrote a lengthy study on that, many decades ago).

So I certainly wouldn't be concerned about applying a TOPICAL antiandrogen to the scalp, like spironolactone, RU58841, fluridil, etc.

Bryan

 

[Fallout Boy]

What are your views on Fluridil and spironolactone?? since RU seems to be really hard to get .. Should a finasteride. / Fluridil or a finasteride. / spironolactone regimen be enough to halt hairloss in most?? OPINIONS?? or point me to a thread related to this ha either one

 

[Bryan]

Since finasteride all by itself is able to halt hairloss in most people, I guess it's safe to say that finasteride/spironolactone or finasteride/fluridil is, too!

I don't have a preference yet when it comes to spironolactone/fluridil. Too little is known about fluridil. I'm waiting for more testing.

Bryan

 

[jimmystanley]

bryan...


Well, keep in mind that men who are castrated can go on to live lengthy lives, although all the effects of having drastically reduced androgen levels are still in a certain amount of doubt (James Hamilton wrote a lengthy study on that, many decades ago).

So I certainly wouldn't be concerned about applying a TOPICAL antiandrogen to the scalp, like spironolactone, RU58841, fluridil, etc.

Bryan

okay..thanks bryan...although i'm not so much worried about reduced androgen levels in the body (since i plan to almost cut out finasteride) Just in those cells that DEMAND androgens. I just wondered if there might be some other effect ...but looks like we're good to go with anti androgens

 

[S Foote.]

bryan...

1. you talk about sensitive cells that cause male pattern baldness as being the ones with 'negative effects' on hair growth factors. Is this the part of male pattern baldness that we know nothing about, or could you give us a further explanation on why there are negative effects instead of positive ones (subjective positive) (or point us to where we can learn more)

Yep, that's the part of male pattern baldness that we know nothing about. Nobody yet understands the "paradoxical" effect of androgens on hair follicles (why they stimulate growth in most body hair follicles, but suppress growth in most scalp hair follicles). Scientists are working on that puzzle as we speak.

But i've already explained it to you Bryan!!

Well one things for sure Bryan, as demonstrated by this thread, the current `direct' action of DHT can't answer the questions!!

You say, quote:

"Consider two very different types of human hair follicles: a beard follicle, and a frontal scalp hair follicle from a balding person. They have several of the same characteristics, including the following: They both have plenty of 5a-reductase. They both have lots of androgen receptors. They both have steroid sulfatase enzymes (which cleave inactive sulfated steroids into their active components), and other enzymes which help convert weaker androgens into more potent androgens.

And yet those two different hair follicles have totally different RESPONSES to androgens! Androgens make beard follicles nice and big and healthy, but they make frontal scalp follicles...well, you already know what they do to scalp follicles! When I talk about different "sensitivities" to androgens that different guys have, I'm not really referring to different numbers of androgen receptors or different amounts of 5a-reductase, I'm mainly referring to those different types of RESPONSES to androgens. See what I mean??"

I take issue here with your comment quote:

"When I talk about different "sensitivities" to androgens that different guys have, I'm not really referring to different numbers of androgen receptors or different amounts of 5a-reductase, I'm mainly referring to those different types of RESPONSES to androgens. See what I mean??"



The in-vito studies clearly show that follicles destined to become male pattern baldness follicles, do `NOT' `directly' RESPOND' to exposure of androgens by turning into male pattern baldness follicles!

You keep on trying to claim that they do in threads like this, but i have asked you time and time again to show us some evidence for this, and you can't!!

To keep on preaching this doctrine on these forums without any evidence, is just misleading people!

S Foote.

 

[jimmystanley]

bryan...

follicles destined to become male pattern baldness follicles, do `NOT' `directly' RESPOND' to exposure of androgens by turning into male pattern baldness follicles!

S Foote.

so this means at the time we get androgen activity in our scalp it does not trigger certain follicles to become male pattern baldness follicles? if so is it because they are already male pattern baldness follicles?

 

[Bryan]

I take issue here with your comment quote:
{snip}
The in-vito studies clearly show that follicles destined to become male pattern baldness follicles, do `NOT' `directly' RESPOND' to exposure of androgens by turning into male pattern baldness follicles!

No, not while sitting overnight in a petri dish. But they _may_ do it gradually over a period of YEARS, just as certain cancer cells slowly change their response to androgens, once they've been deprived of them for several generations...

You keep on trying to claim that they do in threads like this, but i have asked you time and time again to show us some evidence for this, and you can't!!

To keep on preaching this doctrine on these forums without any evidence, is just misleading people!

I have told you REPEATEDLY that I don't claim to have any proof of what causes that change, but you keep parroting that same silly statement. At the moment, I don't care all that much WHY they eventually become androgen-sensitive, I only care that they DO become androgen-sensitive, for whatever reason(s). You need to stop harping on what is essentially a moot point. It doesn't behoove you in any way. It only makes you appear shrill and strident.

Bryan