Local vs Systemic DHT

[michael barry]

Im testing things that could possibly block the androgen receptors........................that should decrease beard hair where applied. Thats my aim.

 

[harold]

Though if this is true
"The investigation of a large
number of genetic variants covering the AR locus suggests
that a polyglycine encoding GGN repeat in exon one is
a plausible candidate for conferring the functional effect.
The polyglycine tract is located in the transactivating domain
of the androgen receptor protein (AR), "
Then it would seem that if Androgenetic Alopecia is driven primarily by such a mutation then the ARs of Androgenetic Alopecia people are not more sensitive as I believed was the case but possibly more prone to be expressed leading to higher levels of ARs in androgen target tissues.

Hmmm....maybe I'm misreading it, but it sounds to me like they ARE talking about more sensitive (or less sensitive) ARs. They're talking about certain encoding repeats "conferring the functional effect", which sounds to me like they mean the overall sensitivity of each AR.

Yeah I'm not sure. I did a little reading on the "transactivating domain" idea and it seemed to be something that was more tied to expression of a gene than anything else. Which I have to admit was what I was looking to find since that just makes more sense to me - we know androgen receptors seeem to be more plentiful in balding scalp. And it would fit with the scenario I gave above as to why there is more DHT in those regions also and the Hoffman/Happle observation.
If they are more sensitive than I wonder how that might effect the HPTA axis - one might suspect it would tend to drive down testosterone/DHT levels proportionally. Yet if anything men with Androgenetic Alopecia have higher androgen levels in serum.
What do you think?

Do you have any links to those studies? It sounds interesting.

Sorry, but I don't. As far as I know, Sawaya has STILL not actually published her infamous finding about the "intense upregulation" of androgen receptors in finasteride users. She only happened to mention that at a news conference at a medical conference several years ago.

The Happle & Hoffmann study was published in the book Hair Research fo the Next Millenium. As far as I know, it hasn't been published in a medical journal. I've cited that study several times over the years, because it has some very interesting and useful stuff in it. I've even used it more than once as ammunition against Stephen Foote! :mrgreen: I really should scan it and post it so that the rest of you can read the whole thing...it's not terribly long, and it reads fast.

OK. Interesting that it was never published. I think I remember a bunch of alt.baldspot people were very worried by that possibility. If the other stuff is in a book then its probably off my radar. I'm too lazy to go to the library except in electronic form
hh

 

[harold]

On that whole sensitivity vs expression thing. This quote from a study on triplet repeats in the gene for the AR in female pattern hair loss talks about changes in both expression levels and function.
"Androgens exert their effect via the androgen receptor (AR)
gene, this contains a highly polymorphic trinucleotide repeat
(CAGn). The length of this repeat affects both AR expression
and function. The number of CAG repeats inversely
correlates with androgen levels and has been associated
with hirsutism and male balding."
As you can see they also claim that the more active/expressed forms go along with higher androgen levels. Will have to read up more to see where that was shown.
The thing is that these guys are talking about a different repeat to the polyglycine one that the other group talks about. There is a paper out that found no association betweeen the polyglycine variations and male pattern baldness.
hh

 

[Bryan]

Yeah I'm not sure. I did a little reading on the "transactivating domain" idea and it seemed to be something that was more tied to expression of a gene than anything else. Which I have to admit was what I was looking to find since that just makes more sense to me - we know androgen receptors seeem to be more plentiful in balding scalp. And it would fit with the scenario I gave above as to why there is more DHT in those regions also and the Hoffman/Happle observation.

If they are more sensitive than I wonder how that might effect the HPTA axis - one might suspect it would tend to drive down testosterone/DHT levels proportionally. Yet if anything men with Androgenetic Alopecia have higher androgen levels in serum.
What do you think?

I agree with you that more sensitive androgen receptors would drive down testosterone/DHT levels proportionally. I don't consider it to be in any way paradoxical that men with Androgenetic Alopecia tend to have somewhat higher serum androgen levels than non-balding men; I think the simple explanation is that they (balding men) have a genetically higher "set-point" for androgens (on average, of course) than non-balding men. In other words, their androgen levels would be even higher than they ALREADY are, were it not for those more-sensitive androgen receptors.

 

[el_duterino]

I am going to try a DHT gel called Andractim & rub it on my Penis to see if libido will improve.
Eventually some of this DHT will end up in my blood since this product is trans-dermal.
My question to you all : In the line of this discussion on local vs. systemic DHT, would this systemic DHT influence hairloss ?

I am also applying topical flutamide twice a day to limit the effects of DHT on the follicules, and taking oral dutasteride 0.5 mg a day to lower DHT overall.
I also started topical dutasteride, after a few weeks I will eas out on oral dutasteride.

My new approach is to be more aggressive at the local ends. Increase DHT in the sexual parts, decrease DHT on the scalp.

Any thoughts ?
Thanks
El Duterino

 

[Bryan]

On that whole sensitivity vs expression thing. This quote from a study on triplet repeats in the gene for the AR in female pattern hair loss talks about changes in both expression levels and function.
"Androgens exert their effect via the androgen receptor (AR)
gene, this contains a highly polymorphic trinucleotide repeat
(CAGn). The length of this repeat affects both AR expression
and function. The number of CAG repeats inversely
correlates with androgen levels and has been associated
with hirsutism and male balding."
As you can see they also claim that the more active/expressed forms go along with higher androgen levels.

I'm not absolutely sure that that's what they're saying, Harold!

They said in that last sentence that the number of CAG repeats INVERSELY correlates with androgen levels, and (presumably) INVERSELY correlates with balding (that second part was also demonstrated in another study). If fewer CAG repeats result in less active androgen receptors, then it makes sense that there would be higher androgen levels. I would also assume in that case that the higher androgen levels are apparently more important in balding than the less active receptors. All of this is pretty confusing and uncertain.

 

[Bryan]

I am going to try a DHT gel called Andractim & rub it on my Penis to see if libido will improve.

Hey, the harder you rub it, the more effective it'll be! :mrgreen:

Eventually some of this DHT will end up in my blood since this product is trans-dermal.
My question to you all : In the line of this discussion on local vs. systemic DHT, would this systemic DHT influence hairloss ?

It _could_ do that, if you apply a high enough dose.

 

[harold]

On that whole sensitivity vs expression thing. This quote from a study on triplet repeats in the gene for the AR in female pattern hair loss talks about changes in both expression levels and function.
"Androgens exert their effect via the androgen receptor (AR)
gene, this contains a highly polymorphic trinucleotide repeat
(CAGn). The length of this repeat affects both AR expression
and function. The number of CAG repeats inversely
correlates with androgen levels and has been associated
with hirsutism and male balding."
As you can see they also claim that the more active/expressed forms go along with higher androgen levels.

I'm not absolutely sure that that's what they're saying, Harold!

They said in that last sentence that the number of CAG repeats INVERSELY correlates with androgen levels, and (presumably) INVERSELY correlates with balding (that second part was also demonstrated in another study). If fewer CAG repeats result in less active androgen receptors, then it makes sense that there would be higher androgen levels. I would also assume in that case that the higher androgen levels are apparently more important in balding than the less active receptors. All of this is pretty confusing and uncertain.

I am fairly sure though that the number of CAG repeats inversely correlates with both balding and androgen levels as you say but the variants with less repeats were what have been referred to by others at least as the more sensitive type. I would assume therefore that they would also be the more numerous since we see more androgen receptors in balding scalps. After that and in the light of the other findings on this thread - confusion.
hh