Androgen-dependent regulation of androgen nuclear receptor in the rat ventral prostate

Methods have been developed for the measurement of nonradioactive or radioactive dihydrotestosterone (DHT) bound to androgen receptor in rat ventral prostate nuclei (DHTRn). Using 1-day-castrated adult Sprague-Dawley rats (300--320 g body weight), the effects of testosterone (T) on nuclear androgen receptor formation were investigated in the absence and presence of cycloheximide or emetine. DHTRn was measured 4 h after injection of increasing amounts of T, and a maximal value of 14.6--17.8 pmol DHTRn/prostate was reached with doses of T greater than 37.5 micrograms. The amount of DHTRn 30 min after administration of 75 micrograms T was already 3 times greater than the concentration of cytosol receptor initially present in untreated castrated rats (2.0 +/- 0.3 pmol/prostate). In rats that received 2 mg cycloheximide ip 30 min before T, DHTRn did not exceed 5 pmol/prostate; in rats pretreated with 10 mg emetine administered at 1 h and 15 min before T, DHTRn did not exceed 8 pmol/prostate. These results suggest a two-component mechanism: 1) the translocation of preexisting cytosolic-receptor-hormone complexes to the nucleus; and 2) de novo formation of androgen receptor dependent on protein synthesis, which upon interaction with exogenous steroid is likewise accumulated in the nucleus. Progesterone (1 mg) and estradiol (0.6 mg) were also injected in amounts calculated to produce the same degree of occupancy of androgen receptor sites as did T. With both of these steroids, nuclear accumulation of androgen receptor was observed, but neither progesterone nor estradiol induced de novo synthesis of androgen receptor.