Mechanisms of action of androgens and antiandrogens: effects of antiandrogens on translocation of cytoplasmic androgen receptor and nuclear abundance of dihydrotestosterone.

The effects of antiandrogens on the translocation of androgen receptor and the accumulation of nuclear dihydrotestosterone in rat ventral prostate were investigated. Using an isotope-exchange assay and radioimmunoassay it was found that 1 hr after the injection of 70 nmol of dihydrotestosterone into 1-day castrated rats, 19,000 +/- 2.350 (mean +/- SE) receptor molecules and 99,300 +/- 8,200 molecules of dihydrotestosterone were recovered per nucleus. When equivalent doses of antiandrogens were substituted for dihydrotestosterone only 0-1,500 receptor molecules were translocated. After injection of antiandrogens followed 1 hr later by injection of dihydrotestosterone, the inhibition of translocation given by the reduction in the mean numbers of molecules of receptor and dihydrotestosterone, respectively, was as follows: 17 beta-estradiol (0, 0); megestrol acetate (2000, 0); diethylstilbestrol (6000, 4000); cyproterone acetate (5500, 27000); flutamide (10000, 29000); R2956 (10000, 28000). With the exception of the effect of cyproterone acetate on receptor translocation, the reductions produced by the latter three antiandrogens were all statistically significant (P less than 0.5). Since less than 20% of the dihydrotestosterone in the nucleus is bound to receptor in dihydrotestosterone-treated rats, and since the concentrations of receptor and dihydrotestosterone are unequally affected by some antiandrogens, we infer that the nuclear abundance of dihydrotestosterone may be regulated in part through nonreceptor-mediated processes.