Numerous AAS that have low binding to the AR in muscle seem to be highly supressive. How is that possible? Are these in effect SARMs in that they have low affinity to the AR in muslce but higher affinity to AR in the hypothalamus? Otherwise how does the HPTA network detect these and shut down (or reduce) the body's own Testosterone production?

Do said androgens or their metabolites also act as progestins or estrogens?

different structures have different binding affinities....DHT does virtually nothing in muscle, but loves the prostate, skin and hair, and does bind to the ARs in the hypothalamus, although i dont believe it's with a whole lot of affinity (that based on its relative proviron not having much impact there...)

and like Heavy said, anything estrogenic or progestagenic will suppress, too, without being anabolic.

A better question might be why are AAS with poor muscle AR binding hypertrophic?

Realize that DHT's lack of effects in muscle are because it doesn't get to the AR intact -- 3-alpha hydroxysteroid dehydrogenase.

Regulation of hormone levels works through various mechanisms -- SupremeDan's threads on testosterone activation of opiate pathways comes to mind.

Anything that decreases LH/FSH is causing shutdown to some degree, and tons of stuff can do that.

Better question indeed...
Would you like to speculate Mr. Tesla?

Muscle AR or AR in general? I think the AR Affinity doesn't vary between different organs, but the differences are:

1) Some androgens can get to the ARs of an organ but not to the ARs of other organs because they are deactivated (as it happens with DHT).

2) Some androgens (like DHT) go through an enzymatic conversion that makes them stronger, but there are organs which lack that enzyme (like skeletal muscle), while there's plenty of it in others (prostate, scalp, ...).

3) Once bound to the AR, not all androgens behave the same way and there are differences between them as far as the genes they tend to activate are concerned (i.e. some tend to activate genes related to muscle hypertrophy, others tend to activate genes related to male pattern baldness, ...).

4) There seem to be some non-AR-mediated mechanisms that play a role. I couldn't elaborate about them, because I lack the knowledge.


Finally, to answer your question more specifically, just imagine an androgen with a low AR binding affinity. Now imagine that androgen has a very low SHBG affinity, its structure offers plenty protection against 3HSD deactivation (a very important feature in any androgen from my point of view) and due to 17-alpha-alkylation it remains in its active form, without being metabolized into inactive compounds and excreted. Wouldn't you think that androgen could be considerably anabolic even when its AR affinity is low?