Androgen receptor agonist efficacy of different AAS

[HUGE McBIGLARGE]

I have never seen this question asked before:

Do different androgens (including AAS) have different efficacies at the androgen receptor?

I am aware of an androgenicity/anabolism ratio. I am aware that some androgens have more binding affinity at the androgen receptor. But neither of these explain the efficacy at the androgen receptor.

I want to know that if you were to flood the body with enough of any particular androgen, would there be a marked difference in androgenicity? In other words, if I took 10 kilograms of testosterone, or DHT, or anavar, or primobolan, and therefore every androgen receptor was always bound by the respective androgen, would the pro-androgenic effects induced by stimulation of the androgen receptor be the same?

I can’t find any answers to this on Google. I have battled with ChatGPT and it is trying to gaslight me into believing that all androgens (including testosterone and DHT) are equally efficacious at inducing androgen receptor agonism; the only differences are how easily they bind to the receptor (affinity), how long they remain bound, and peripheral reduction in the case of reducible androgens. ChatGPT’s sources for this assertion are absolutely shit, yet I can never get it to stop making this assertion.

This is an important question, in my opinion, as if not all androgens share the same efficacy at the androgen receptor, then it is possible to reduce total androgenicity by the addition of more AAS via competition at the androgen receptor. At least in theory.

 

[bananafeet]

Androgenicity as far as I'm aware means "to make male". So that's the development of the penis, lowering of the voice, increasing the amount of body hair.

DHT is not anabolic because of reduction by 3aHSD in muscle tissue. However it contributes to anabolism indirectly by increasing motivation and neural drive. In human makes it is the steroid that causes the characteristic male features.

Source: Steroid 5agr-Reductase Deficiency in Man: An Inherited Form of Male Pseudohermaphroditism | 10.1126/science.186.4170.1213_Sci-hub
"The data suggest that there may be
at least two androgens involved in sex-
ual differentiation, with selective roles
for testosterone and dihydrotestosterone
during embryogenesis. The male pseu-
dohermaphrodites described below de-
fine the necessity for dihydrotestos-
terone during embryogenesis and de-
lineate the actions of testosterone and
dihydrotestosterone in sexual differen-
tiation and development."

Anyhow. I don't think AR signalling is the limiting factor. It's more likely metabolism that limits anabolism.

As for the most potent AR signalling. There are side effects to activating the AR for extended periods of time. Testosterone doesn't stay bound for as long as other androgens, but still contributes to muscle protien synthesis. So the real question is which androgen or anabolic steroid contributes the most to MPS or genomic action.

It's probably testosterone. Because unlike other steroids it also is pro hormone to E2 which upregulates IGF1 and AR expression and DHT which increases neural drive.

All other steroids would have their rate limit not at the AR but in other metabolic pathways.

Anyway that's my theory.

 

[drolonaguy]

This is a fascinating topic although taking decisions based on it it's quite hard. First you have the direct action at the AR, then also the surface translocation that probably depends on factors like membrane composition, and the small but relevant effect of bound androgens on a receptor that I don't remember the name.