Effects of a non-steroidal antiandrogen on sexual behavior and pituitary-gonadal function in the male rat.

An investigation was conducted on the effects of the non-steroidal antiandrogen flutamide (F; alpha-alpha-alpha-tri-fluoro-2-methyl-4-nitro-m-propionotoluidide) on two neuroendocrine mechanisms in the male rat, androgen-dependent sexual behavior, and LH regulation. F was administered in the dose of 50 mg/kg/day SC. In intact, sexually experienced adult males, no quantitative or qualitative behavioral effects were noted. In long-term castrates, F completely suppressed the effects of 100 mug testosterone propionate (TP) per day on accessory sexual glands and penes, but only partially inhibited the marked stimulatory effects of this moderate TP dose on mating. Although the incidence of testosterone (T)-activated ejaculatory behavior was markedly diminished, there was no statistically significant effect on occurrence of mount and intromission behavior. The rapid and profound elevations of circulating LH and T in intact males indicate an effective antagonism of the negative feedback effect of endogenous androgen, and suggest the usefulness of F as a provocative test of pituitary-testicular function. Pituitary LH response to exogenous LHRH was markedly enhanced, as previously found in castrated rats. The administration of F did not affect circulating T levels in T-treated or untreated castrates, indicating lack of interference of circulating F in the T assay. It was concluded that, like the steroidal antiandrogen cyproterone, non-steroidal F shows a divergence between its effects on peripheral androgen-dependent and central feedback mechanisms on the one hand, and sexual behavior on the other. It was not determined whether the inhibition of ejaculatory behavior following F treatment is centrally mediated or results from failure of the peripheral, androgen-dependent structural or functional elements.