Action of prolactin in regressing prostate: independent of action mediated by androgen receptors.

Hyperprolactinemia, achieved by grafting pituitaries under the renal capsule, has been shown to cause a delay in the rate of castration-induced prostatic regression in rats. The mechanism of this prolactin action is not established, although it has been suggested that the action of prolactin in the rat prostate is mediated through the action of androgen. To explore the possibility that a small amount of residual endogenous androgen present in the prostate at the time of castration acts synergistically with prolactin to cause this delay in prostatic regression, Flutamide has been used in the present study in an attempt to inhibit this residual androgen effect by blocking its interaction with androgen receptors. Two experiments were conducted. In experiment 1, daily sc injections of Flutamide (25 mg/kg) for 7 days to castrated rats supplemented with dihydrotestosterone-filled silastic tubing either 1 or 4 cm long completely suppressed both prostatic weight and protein content to the level that was normally observed in castrated rats receiving empty tubings. Furthermore, treatment of Flutamide to castrated rats did not cause an increase in prostatic weight and protein content over those of castrated rats treated with the vehicle only. These results indicate that Flutamide, at this dosage, is a potent antiandrogen and that the compound itself does not have any androgenic activity in the rat prostate. In experiment 2, adult male rats were castrated and received two female pituitaries grafted under the renal capsule. One week later, their serum prolactin levels increased from 20 +/- 3 ng/ml to 102 +/- 8 ng ml. This elevated level of serum prolactin was associated with a delay in the rate of prostatic regression. Administration of Flutamide, at a dose (25 mg/kg) which completely suppressed prostatic growth, failed to inhibit the delay in prostatic regression in castrated rats bearing the pituitary grafts. Since Flutamide inhibits the androgen action in the prostate by blocking the binding of intracellular dihydrotestosterone to androgen receptors, the failure of Flutamide to block the effect of prolactin suggests that the prolactin action in regressing prostates is not mediated by androgen receptors.