Androgen receptor dynamics in the rat ventral prostate.

Upon testosterone administration, a dose-dependent cytosolic depletion and nuclear accumulation of androgen receptors in the ventral prostate of 1-day-castrated male rats is observed. Replenishment in the cytosol is rapid with a return to control levels 3 h after testosterone stimulation. The process of nuclear retention (as measured 4-6 h post-injection) is both dose-dependent and time-dependent (there is no retention of the androgen receptor 15 h after testosterone). When assayed 1 h after testosterone, the increase in nuclear binding sites was not sufficient to conclude that the disappearance of cytosolic binding sites could be accounted for by translocation of cytosolic receptors to the nucleus. The cytosolic compartment contained more than 70% of the total cellular receptors whether testosterone was present (in the range 50-400 micrograms/100 g body wt.) or not. Nuclear processing of androgen receptors is extensive and it is dose-dependent. Turnover of prostatic androgen receptors was studied simultaneously in the cytosolic, microsomal and nuclear compartments 1, 2, 3, 4, 5 and 6 h after testosterone administration. Cytosolic and microsomal depletion-replenishment patterns are similar, displaying a nadir after 1 h and a full replenishment 3-4 h post-testosterone. Cycloheximide, but not actinomycin D, inhibits cytosolic and microsomal replenishment. Nuclear accumulation and retention of androgen receptors is insensitive to both drugs. The very rapid and RNA synthesis-independent turnover of androgen receptors in the ventral prostate suggests that testosterone regulates the receptor levels acutely by both a rapid post-transcriptional positive action and a similarly rapid negative effect on nuclear receptor half-life.