What Does Ar(androgen Receptor) Sensitivity Means?

[Mandar kumthekar]

Recent studies have concluded that AR gene can explain 40%risk of baldness. It is higher risk for any signal gene. Androgen receptor gene which we inherites from mother is crucial.
My question is about androgen sensitivity concept. What do researchers mean when they say "androgen sensitivity "mediated by AR gene. Does particular AR gene variant in bald people codes for Androgen receptors to which DHT binds in large amount than other variants?
What defines AR sensitivity?
If bald people have androgen receptors which binds to more DHT than normal then why don't they are more masculine and healthy if androgen masculinization is imp for men?. The myth that bald men are more viril is actually true ? Seems likely if we accept AR sensitivity concept.

 

[justlol@you]

as far as I'm aware "sensitivity" theories originated from forums, not scientific research.

 

[Mandar kumthekar]

as far as I'm aware "sensitivity" theories originated from forums, not scientific research.

So what did various members on different forum mean when they say androgen sensitivity? Had anyone came up with moleculer mechanism?

 

[Trichosan]

So what did various members on different forum mean when they say androgen sensitivity? Had anyone came up with moleculer mechanism?

Probably not and if they did they wouldn't be able to come up with a way to genetically neutralize it harmlessly. Thus, we are fucked in the *** for the foreseeable future.

 

[lemoncloak]

@Mandar kumthekar
Wikipedia:

CAG repeats

The AR gene contains CAG repeats which affect receptor function, where fewer repeats leads to increased receptor sensitivity to circulating androgens and more repeats leads to decreased receptor sensitivity. Studies have shown that racial variation in CAG repeats exists,[36][37] with African-Americans having fewer repeats than non-Hispanic white Americans.[36] The racial trends in CAG repeats parallels the incidence and mortality of prostate cancer in these groups.


Also look at this https://en.m.wikipedia.org/wiki/DNA_methylation especially the parts about CpG

 

[Mandar kumthekar]

Probably not and if they did they wouldn't be able to come up with a way to genetically neutralize it harmlessly. Thus, we are fucked in the *** for the foreseeable future.

If we could find entire molecular mechanism then I don't think solution would be far ahead. We don't know it so we can't solve it.that's it. I only wanted to know about the sensitivity concept which has been floating and chanted million times.

 

[Mandar kumthekar]

@Mandar kumthekar
Wikipedia:

CAG repeats

The AR gene contains CAG repeats which affect receptor function, where fewer repeats leads to increased receptor sensitivity to circulating androgens and more repeats leads to decreased receptor sensitivity. Studies have shown that racial variation in CAG repeats exists,[36][37] with African-Americans having fewer repeats than non-Hispanic white Americans.[36] The racial trends in CAG repeats parallels the incidence and mortality of prostate cancer in these groups.


Also look at this https://en.m.wikipedia.org/wiki/DNA_methylation especially the parts about CpG

AR receptors are same throughout the body. So if African Americans have fewer CAG repeats in AR and are thus sensitive to androgens then we would have had the reverse observation that is more African Americans were bald then than European whites. But that is not the case. CAG repeats negatively correlate to transcription activity of AR gene but that doesn't shows up in studies. They found weak correlation.

 

[lemoncloak]

AR receptors are same throughout the body. So if African Americans have fewer CAG repeats in AR and are thus sensitive to androgens then we would have had the reverse observation that is more African Americans were bald then than European whites. But that is not the case. CAG repeats negatively correlate to transcription activity of AR gene but that doesn't shows up in studies. They found weak correlation.

Huh. You're right. I think whoever wrote this got it mixed up and african americans have more CAGs on average, there are articles online about androgen receptor gene methylation if you wanna have a look

 

[Mandar kumthekar]

Huh. You're right. I think whoever wrote this got it mixed up and african americans have more CAGs on average, there are articles online about androgen receptor gene methylation if you wanna have a look

Where I can find that articles?. I generally search ncbi for scholarly articles. If androgenic alopecia is epigentic thing then we could reverse it by epigenomic alteration by diet.

 

[lemoncloak]

AR receptors are same throughout the body. So if African Americans have fewer CAG repeats in AR and are thus sensitive to androgens then we would have had the reverse observation that is more African Americans were bald then than European whites. But that is not the case. CAG repeats negatively correlate to transcription activity of AR gene but that doesn't shows up in studies. They found weak correlation.

No the article quoted says the same. Sth's not right. I might look it up later.
It could be that different areas of the receptor gene affect different body parts.

I wouldn't rely on diets for that. Methylation has to do with proteins (lack of) unfolding to allow transcription to take place, so AR can be produced. It happens in the nucleus so just because it's epigenetic doesn't mean it can be cured by onion or curcumin.

Google androgen receptor gene methylation baldness.
Here's one article https://www.ncbi.nlm.nih.gov/m/pubmed/11231320/
Tackling male pattern baldness through the AR while possible is particularly hard. Either through crispr (which is not there yet and can't ressurect dead dermal papillas) or antiandrogens that target it, since ARs are produced fast (possibly hours) and the body starts making more to offset the meds. Not to mention meds go systemic-> side effects.

Stem cell multiplication (see Tsuji) is the only way I see on the horizon to beat this thing.

 

[Mandar kumthekar]

Have you read any article which says that AR coded by particular gene variants with fewer CAG repeats binds with DHT rigorously than other normal AR variants? Do bald people have more DHT uptake in cell nucleus than others? Do you think that is the case?

 

[bboy]

Can't find the study right now. But recently I was doing some reading around some of the alternate theories of Androgenetic Alopecia, so I was looking for the studies where they took out DP cells and then saw how they interacted with T and DHT. The interesting thing was when they just tried to introduce androgens the cells didn't react, they actually had to induce AR over-expression before cells started to act like Androgenetic Alopecia DP cells.

So, just speculating, it could be that going after the pathway that causes overexpression would be even more effective than reducing DHT, or maybe even going after the AR's themselves. And you'd just need to get them below a certain threshold, normal levels for the DP cells not to act like Androgenetic Alopecia DP cells.

And because you're not actually going after Androgens or AR's directly, the side effects could be lower, and consequently the aggressiveness of the treatment could be much higher.

What that pathway is, how you'd attack it, and what side effects it might cause, I have no idea about though.

 

[Mandar kumthekar]

Thanks for link!

Can't find the study right now. But recently I was doing some reading around some of the alternate theories of Androgenetic Alopecia, so I was looking for the studies where they took out DP cells and then saw how they interacted with T and DHT. The interesting thing was when they just tried to introduce androgens the cells didn't react, they actually had to induce AR over-expression before cells started to act like Androgenetic Alopecia DP cells.

So, just speculating, it could be that going after the pathway that causes overexpression would be even more effective than reducing DHT, or maybe even going after the AR's themselves. And you'd just need to get them below a certain threshold, normal levels for the DP cells not to act like Androgenetic Alopecia DP cells.

And because you're not actually going after Androgens or AR's directly, the side effects could be lower, and consequently the aggressiveness of the treatment could be much higher.

What that pathway is, how you'd attack it, and what side effects it might cause, I have not idea about though.

How did they induce overexpresion in non reactive DP cells?

 

[bboy]

Thanks for link!

How did they induce overexpresion in non reactive DP cells?

Don't know, but here's a another study where they did a similar thing.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828374/

Interestingly, I wasn't aware of this, but even non-Androgenetic Alopecia DP cells start acting like Androgenetic Alopecia DP cells if you pump very high levels androgens around them.

https://www.ncbi.nlm.nih.gov/pubmed/16931898

So is it that only difference between Androgenetic Alopecia and non-Androgenetic Alopecia DP cells is the AR overexpression in the Androgenetic Alopecia DP cells?

 

[Mandar kumthekar]

Don't know, but here's a another study where they did a similar thing.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828374/

Interestingly, I wasn't aware of this, but even non-Androgenetic Alopecia DP cells start acting like Androgenetic Alopecia DP cells if you pump very high levels androgens around them.

https://www.ncbi.nlm.nih.gov/pubmed/16931898

So is it that only difference between Androgenetic Alopecia and non-Androgenetic Alopecia DP cells is the AR overexpression in the Androgenetic Alopecia DP cells?

Fabulous ! Thanks!!
AR over expression is the key then. Few AR variant can easily over expressed them than others and that has to do with their ligand binding domain. I think the mutation in AR which causes early baldness must be in ligand binding domain region of AR gene.