When I use a word like “regulation” in reference to the androgen receptor, we’re talking about control or power over the receptor itself, while “sensitivity” will be used to mean the receptor’s level of activity or action, and “number” will be used to mean…ehh…number. Something that regulates the androgen receptor is a thing that exerts power over the number or sensitivity of the receptor itself, either positively or negatively. Increasing AR sensitivity will allow the same number of receptors to do more work, while increasing the number will give us more receptors to accomplish more work. The opposite will also hold true – a less sensitive receptor (or having less in number) will mean less effect being exerted on the cell.
Half-lives and proliferation of the androgen receptor can vary according to the cells examined – meaning an intense HIIT session might cause a severe uptick in number and sensitivity for skeletal tissue, but less for the scalp or epidermis (the latter having a high concentration of receptors). If we look at muscle tissue, and there’s no ligand (androgen) attached to the receptor, we’re talking about a half-life of about three hours. So if you had two receptors, three hours later you’d have one (arbitrary numbers). And if production rate was one per three hours (again, in the absence of androgen), you’d be in a state of homeostasis with two receptors at all times, one dying off as another was formed. But if you add a ligand into the mix, the half-life more than doubles as does the production rate. Therefore, when people talk about a saturation effect, or receptors being clogged or desensitised, they’re not really painting an accurate picture of what’s happening. Not yet, anyway (or at least not on a typical 12-16 week cycle).
In fact, although they didn’t look at the androgen receptors per se, the classic Bhasin et al study showed a disproportionately greater response with the higher (and highest) doses of testosterone (up to 600mgs/week of a long ester). We can’t say that this was due to the receptor activity (as it wasn’t measured), but we can say that no “clogging” or “desensitising” effect was seen. That study lasted 12 weeks, and it should still be noted that while the greatest results were seen with the highest dose, the majority of those results weren’t seen at the end of the cycle.
In contrast, work by Sheffield-Moore et. al., showed that when older men were given testosterone until their levels reached the higher side of physiological, their AR expression experienced a 200%+ increase after the first month – but after six months had returned to baseline. So again, we’re back to the body being very good at achieving homeostasis, and while a typical cycle won’t cause the downregulation we hear about, any long-term pharmaceutical use will ultimately lose to the body’s ability to regulate itself. Don’t worry though, if you stay off for long enough, you’ll become sensitised again. Just like staying away from caffeine… if you do it long enough, your next double espresso eventually feels like a grande kick in the balls.