Relative potency of antiandrogens with reference to intracellular testosterone in the rat prostate.

Mechanisms of relative potency in direct action of antiandrogens have not been fully elucidated. Using castrated rats, the effects of antiandrogens on the prostatic weight gain induced by exogenous testosterone (T), and on T uptake into prostatic cells were examined. Tested antiandrogens were cyproterone acetate, chlormadinone acetate, a new steroidal antiandrogen, 17acetoxy-6-chloro-2-oxa-4,6-pregnadiene-3,20-dione (TZP-4238), and one nonsteroidal type, flutamide (FL). Suppression of prostatic weight gain, T uptake and serum concentrations of compounds, correlated well each other among steroidal antiandrogens, while FL was five times more active in suppressing weight gain than TZP-4238, associated with a lower nuclear distribution of androgen. The results suggest that 1) suppression of T uptake is a major and common mechanism of steroidal antiandrogens and the relative potency is attributable to pharmacokinetic characteristics in vivo, and 2) FL suppress s nuclear T uptake more specifically than steroidal antiandrogens.