Assimos D, Smith C, Lee C, Grayhack J T
Prostate. 1984;5(6):589-95. doi: 10.1002/pros.2990050604.
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.
通过将垂体移植到肾被膜下诱导的高催乳素血症，已被证明会导致大鼠去势诱导的前列腺退化速率延迟。尽管有人提出催乳素在大鼠前列腺中的作用是通过雄激素的作用介导的，但这种催乳素作用的机制尚未确定。为了探讨去势时前列腺中存在的少量残留内源性雄激素与催乳素协同作用导致这种前列腺退化延迟的可能性，本研究使用氟他胺试图通过阻断其与雄激素受体的相互作用来抑制这种残留雄激素的作用。进行了两个实验。在实验1中，对去势大鼠每日皮下注射氟他胺（25mg/kg），持续7天，这些大鼠补充了1cm或4cm长的填充二氢睾酮的硅橡胶管，结果完全抑制了前列腺重量和蛋白质含量，使其降至接受空管的去势大鼠通常观察到的水平。此外，给去势大鼠使用氟他胺处理，与仅用赋形剂处理的去势大鼠相比，并未导致前列腺重量和蛋白质含量增加。这些结果表明，在此剂量下，氟他胺是一种有效的抗雄激素药物，且该化合物本身在大鼠前列腺中没有任何雄激素活性。在实验2中，成年雄性大鼠被去势并接受两个移植到肾被膜下的雌性垂体。一周后，它们的血清催乳素水平从20±3ng/ml升高到102±8ng/ml。血清催乳素水平的这种升高与前列腺退化速率的延迟有关。以完全抑制前列腺生长的剂量（25mg/kg）给予氟他胺，未能抑制垂体移植的去势大鼠中前列腺退化的延迟。由于氟他胺通过阻断细胞内二氢睾酮与雄激素受体的结合来抑制前列腺中的雄激素作用，氟他胺未能阻断催乳素的作用表明催乳素在退化前列腺中的作用不是由雄激素受体介导的。
