I'm looking for a crazy study....

[CCS]

However, I do not understand why more androgen receptors are being created in a tissue that should not need them. It should be negative feedback, but I don't know why the system seems to be working backwards when it comes to hormonal stimulation.

It's as if androgen stimulation causes more androgen receptors to be created, which amplifies the downstream effects of androgens. This could be the reason why male pattern baldness as a disease is so progressive and seems to accelerate or at least progress rapidly once whatever "signal" is given or physiological obstacle is overcome in the non-male pattern baldness follicle.

I read that balding scalp has an average of twice as many androgen receptors and twice as much DHT as non-balding scalp on the same men. Not sure how authoritative the source was, though. But slick bald scalp has the most DHT of all. There are large variations between men, though, but that is the overall average.

 

[Bryan]

Do you know what enzyme in the liver metabolises DHT and which one testosterone?

You're assuming that there's only ONE such enzyme for each?

I hope they are not metabolised by the p450 enzyme, which metabolises dutasteride, since I'm inhibiting it with grapefruit.

Aromatase IS one of the many p450 enzymes, but I've never heard that it's inhibited by grapefruit. Grapefruit does inhibit the CYP3A4 enzyme, however.

I wish I knew just how effective estrogen is supposed to be for helping hair, and that Bryan's proof is not based on women having more estrogen and more hair, since they also have less testosterone and DHT.

No, it's based on more than just that. It's based on that study which I've posted several times showing that estrogen added to cultured scalp hair follicle cells accelerated their growth. It's also based on that other article which has been posted a few times showing a similar result of estrogen on the scalp of a human test subject. It's also based on the widespread use of topical estrogens for male pattern baldness, mainly in Europe.

Bryan

 

[Bryan]

...I think we need to figure out something that explains the increase in androgen receptors.

Yes, it seems the AR's go haywire for some unknown reason. Too many, too sensitive.....?

Hmmm....other people have always seemed to be a lot more interested in the numbers of androgen receptors than I am! I'm sure that there are somewhat more ARs in balding hair follicles than in non-balding ones, but I don't think that's a particularly important feature of male pattern baldness. In other words, I don't think that's sufficient to explain the difference between balding and non-balding follicles.

Having said that, I will mention again (as I have several times in the past, especially in response to Stephen Foote) the study I have here which measured RNA levels of (among other things) androgen receptors in cultured human scalp hair follicles, when stimulated with added testosterone. Looking at the graph from the study, it looks like added testosterone mildly downregulated androgen receptor RNA, which would seem to go right along with Sawaya's findings of increased AR in finasteride users.

Interestingly, it also found that added testosterone strongly UPregulated the production of 5a-reductase type 2 RNA, while the type 1 version was relatively unaffected.

Bryan

 

[abcdefg]

Um I cant really contribute to any of this, but im curious about what you guys think. What do you think of someone say 20ish using propecia? Do you think its a good idea, safe altering DHT for that long a time period? Is it better to wait for safer DHT inhibitors if you have very minor hairloss?

 

[Old Baldy]

Hey Bryan. I was generalizing about what College alluded to relative to balding men having, on average, more AR's in their pattern loss area than non-balding men. You know, our "starting point" is we have more AR's than non-balding men.

Don't really know if this contributes to male pattern baldness but it does make me wonder. It would be rather ironic, and confusing, if the increased amount of AR's meant nothing.

I mean, is having one AR enough to cause minaturization? Or does it take many? You get what I mean and I don't know the answer.

That's what I was alluding to when I asked you guys if pre-puberty males have less AR's than adult males. I was thinking that there might be a threshold level of AR's needed to cause or develop male pattern baldness?

Do we, on average, have more scalp DHT because we, on average, have more AR's? At first blush, you'd think - yes.

Or do we have a propensity to just plain create more DHT once the AR gets "fertilized" by androgens? Or are our AR's just plain more efficient at delivering androgens to the DP? The questions go on and on and.....on. Part of being wacko I guess.

Same for the 5AR2 enzyme. Do we produce more of this enzyme than non-balding men?

Seems I read info. on these questions but just can't remember one way or the other!!

 

[Bryan]

Hey Bryan. I was generalizing about what College alluded to relative to balding men having, on average, more AR's in their pattern loss area than non-balding men. You know, our "starting point" is we have more AR's than non-balding men.

Don't really know if this contributes to male pattern baldness but it does make me wonder. It would be rather ironic, and confusing, if the increased amount of AR's meant nothing.

I've never meant to imply that I think it's completely irrelevant; it's obviously ONE factor, in addition to many others.

I mean, is having one AR enough to cause minaturization? Or does it take many? You get what I mean and I don't know the answer.

According to a textbook on physiology I have here, a typical cell contains around 3,000 to 10,000 androgen receptors. I suspect that having just one single AR wouldn't be enought to cause miniaturization!

That's what I was alluding to when I asked you guys if pre-puberty males have less AR's than adult males. I was thinking that there might be a threshold level of AR's needed to cause or develop male pattern baldness?

Damn...people sure spend a lot of time worrying about androgen receptors! :shock: I'm still to this day shocked at the firestorm of controversy that started when word first came out about Sawaya's "intense upregulation of androgen receptors" in finasteride users. I barely even batted an eyelash when _I_ first heard about that.

I've never ever seen a study which measured levels of androgen receptors in pre-pubertal children. That would be interesting, I'll admit.

Do we, on average, have more scalp DHT because we, on average, have more AR's? At first blush, you'd think - yes.

Or do we have a propensity to just plain create more DHT once the AR gets "fertilized" by androgens?

Are you referring to the study I cited above? It suggests that the answer to both questions would probably be yes, since androgenic stimulation (at least in the form of testosterone) caused an upregulation of 5a-reductase in hair follicle cells.

Or are our AR's just plain more efficient at delivering androgens to the DP? The questions go on and on and.....on. Part of being wacko I guess.

Same for the 5AR2 enzyme. Do we produce more of this enzyme than non-balding men?

Probably "yes" to both questions, but I want to emphasize again that I personally am more interested in the QUALITATIVE differences in the response to androgens from one man to another, not just the QUANTITATIVE differences. Instead of merely wondering why one man (a balding man) has a few more androgen receptors and a little more 5a-reductase than his non-balding neighbor, why don't we invest more time and energy in figuring out why androgens actually stimulate the growth of most body hair, but suppress the growth of scalp hair? Wouldn't that be the ultimate secret of all?? :wink:

Bryan

 

[Old Baldy]

Ok Bryan, thanks for the info. Never knew the average cell has 3,000 to 10,000 AR's! Puts things into proper perspective if you know what I mean.

Bryan wrote in part:

Instead of merely wondering why one man (a balding man) has a few more androgen receptors and a little more 5a-reductase than his non-balding neighbor, why don't we invest more time and energy in figuring out why androgens actually stimulate the growth of most body hair, but suppress the growth of scalp hair? Wouldn't that be the ultimate secret of all??

Yes!

Body hair follicles produce growth factors when "hit" with androgens. Pattern loss follicles produce inhibitory(sp?) growth factors when "hit" by androgens. WHY!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!?

Or let me put it another way - WHY?!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!

 

[Guest]

Looking at the graph from the study, it looks like added testosterone mildly downregulated androgen receptor RNA, which would seem to go right along with Sawaya's findings of increased AR in finasteride users.

Interestingly, it also found that added testosterone strongly UPregulated the production of 5a-reductase type 2 RNA, while the type 1 version was relatively unaffected.

Bryan

Can you dumb this down for the laypeople on here?

 

[CCS]

Yeah, there is conflicting info. Testosterone ups and downs the amount of 5ar.

 

[abcdefg]

It is funny how if I pull on say hair by my belly button as hard as I can it doesnt budge at all, yet a very gentle tug on my scalp hair and lots of em come out. Something is just plain not right, its a simple observation, but you know it has a very complex answer. The difference between hairs reaction to androgens is definately important. There is more to it then simply androgens thats for sure.

 

[abcdefg]

One more stupid non scientific observation from me then ill shutup. DHT clearly is very important though. I mean propecia is a large step forward in our understanding. I mean obviously it doesnt take an idiot to observe that most women at age 50 have very thick hair. They look like they havent lost any hair at all. I mean the major difference between a man and a women is sexual and that is hormonal so propecia is definately a very major step. I am atleast right about that right?

 

[Bryan]

Looking at the graph from the study, it looks like added testosterone mildly downregulated androgen receptor RNA, which would seem to go right along with Sawaya's findings of increased AR in finasteride users.

Interestingly, it also found that added testosterone strongly UPregulated the production of 5a-reductase type 2 RNA, while the type 1 version was relatively unaffected.

Bryan

Can you dumb this down for the laypeople on here?

Adding testosterone to scalp hair follicles in vitro caused them to produce a little fewer androgen receptors, considerably more 5a-reductase type 2, and didn't have much effect at all on 5a-reductase type 1.

Bryan

 

[Old Baldy]

Bryan: Do you believe in the "naked ape" (or "aquatic ape") theory?

I can't think of any better one.

 

[Guest]

Looking at the graph from the study, it looks like added testosterone mildly downregulated androgen receptor RNA, which would seem to go right along with Sawaya's findings of increased AR in finasteride users.

Interestingly, it also found that added testosterone strongly UPregulated the production of 5a-reductase type 2 RNA, while the type 1 version was relatively unaffected.

Bryan

Can you dumb this down for the laypeople on here?

Adding testosterone to scalp hair follicles in vitro caused them to produce a little fewer androgen receptors, considerably more 5a-reductase type 2, and didn't have much effect at all on 5a-reductase type 1.

Bryan

Gotcha. And what are the implications of this with regard to possible increased scalp testosterone levels on dutasteride?

 

[Old Baldy]

Bryan: I forgot to ask you (after my "leftfield" question about the naked ape theory) whether Retin-A's ability to reduce the amount of AR's is beneficial in your opinion?

I need a "perspective" on AR's, I'm having a difficult time figuring out the importance ( of lack of importance) of diminishing their numbers. Although, when you told me the range of AR amounts in cells it became a little clearer that the change would have to be rather DRAMATIC I assume?

Doctor asked about Retin-A in another forum and I remembered I forgot to ask you about this.

Also, do you know the amount of AR's in the cells of a non-balding man versus a balding man?

 

[CCS]

I think bryan said he does not think the number of AR's matters, though maybe he just meant in the context of a treatment changing the number by a small amount.

I read on a site as credible/uncredible as baldingblog that balding men have twice as many AR's and twice the DHT in the scalp as non-balding men. Maybe Bryan has a more authoritative answer.

 

[CCS]

Does retinol actually reduce AR numbers? and by how much?

Is that just another Lee tale?

 

[Old Baldy]

Does retinol actually reduce AR numbers? and by how much?

Is that just another Lee tale?

Retin-A reduces AR numbers. It's "fact" based on some studies that haven't been refuted as far as I know. The studies are not new.

Bryan wants to know why body follicles respond favorably to androgens while scalp follicles respondly badly. AR's probably don't have alot to do with answering that question. That question goes deeper. To me, that's a "genetic" type of question.

 

[CCS]

so does that mean minoxidil with retinol may be better? I'd use very dilute retinol, or course. Get a $10 ounce of retinol from lee, and really dilute it minoxidil, to like 0.001% or something. Cheap. I heard too much can be bad. How much is needed to reduce the number of AR's?

 

[Old Baldy]

so does that mean minoxidil with retinol may be better? I'd use very dilute retinol, or course. Get a $10 ounce of retinol from lee, and really dilute it minoxidil, to like 0.001% or something. Cheap. I heard too much can be bad. How much is needed to reduce the number of AR's?

I use a cream separate from all other applications about 2 to 3 times a week. Any common concentration is good from what I've read.

I have two strengths: 0.05 percent and 0.1 percent creams. Most people use 0.025 percent but I'm old and have a "harder" scalp to treat.

Imagine our male pattern baldness scalps are concrete. You young guys have "baby" concrete. I, being old, have "Hitler bunker" type of concrete. That's why I use the strong stuff.

My skin peeled so much when I first started using Retin-A that I bet every member at this site that I was the champion peeler!! Never had irritation using it 2-3 times a week but, my God, did I PEEL!!!!