Science Peeps - Antiandrogens Mechanism of Action

[potatopirate]

I have a pretty good understanding of how AR inhibitors function, and I have a mild idea of what topical anti-androgen's do, but I am curious

Why does DHT/T damage hair when it binds to the receptor site, but for example RU doesn't? And other topical anti androgen's, why do they not harm the hair when they bind to it?

 

[BigBadBaldie]

I have a pretty good understanding of how AR inhibitors function, and I have a mild idea of what topical anti-androgen's do, but I am curious

Why does DHT/T damage hair when it binds to the receptor site, but for example RU doesn't? And other topical anti androgen's, why do they not harm the hair when they bind to it?

My understanding is that androgens don’t “damage the receptor” exactly, they enable genetic transcription which programs the hair follicle to become dormant. An anti androgen occupies the receptor site blocking this genetic transcription but is designed in such a way that it occupies but does not trigger genetic transcription.
My understanding could be wrong but from what I know that’s how it works.

 

[BetaBoy]

I have a pretty good understanding of how AR inhibitors function, and I have a mild idea of what topical anti-androgen's do, but I am curious

Why does DHT/T damage hair when it binds to the receptor site, but for example RU doesn't? And other topical anti androgen's, why do they not harm the hair when they bind to it?

NSAA‘s have several different modes of action depending on the drug, ultimately though they all prevent the AR from binding to DNA to transcribe AR target genes.

 

[OtyMac]

I have a pretty good understanding of how AR inhibitors function, and I have a mild idea of what topical anti-androgen's do, but I am curious

Why does DHT/T damage hair when it binds to the receptor site, but for example RU doesn't? And other topical anti androgen's, why do they not harm the hair when they bind to it?

The whole concept of antagonism is finding things that bind to the receptor with less biological action than what you desire. So, in this case, we are occupying the androgen receptor with something with less androgenic action than dht which wouldn't be that hard to find a molecule to do that.

You can occupy the available androgen receptors with a lame duck molecule so dht is jammed with no where to park. There are only so many "parking spaces", right? Well, the cell responds back and adjusts receptor numbers too the "parking lot" is never stagnant so there is always a feedback "battle:" occurring in the cell/"parking lot"<chuckle>

There was a study I read recently about phytoestrogens and their estrogen effect was something like 400,000th times less.

 

[Norwoody]

Experimentality put it well. He said that the nucleus is a house. When DHT binds to the cell’s receptor, DHT comes out of the house like a thief, with the genes that direct male pattern baldness. Other substances are like a visitor that comes to your house but don’t take anything out, or at least anything that will harm you.

 

[OtyMac]

The nucleus can never be a house and should ALWAYS be considered a parking lot...hahahahaha

Your analogy was good too, I'm just messing with ya'

 

[pegasus2]

The combination of the two structures does not create the chemical signal that draws it to the nucleus of the cell, so nothing happens. It just sits in the cytoplasm until it is degraded.