Södersten P, Gray G, Damassa D A, Smith E R, Davidson J M
Endocrinology. 1975 Dec;97(6):1468-75. doi: 10.1210/endo-97-6-1468.
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.
研究了非甾体类抗雄激素氟他胺（F；α-α-α-三氟-2-甲基-4-硝基间丙酰甲苯胺）对雄性大鼠两种神经内分泌机制、雄激素依赖性性行为和促黄体生成素（LH）调节的影响。F以50mg/kg/天的剂量皮下注射。在完整的、有性经验的成年雄性大鼠中，未观察到定量或定性的行为影响。在长期去势的大鼠中，F完全抑制了每天100μg丙酸睾酮（TP）对附属性腺和阴茎的作用，但仅部分抑制了该中等剂量TP对交配的显著刺激作用。虽然睾酮（T）激活的射精行为发生率明显降低，但对爬跨和插入行为的发生没有统计学上的显著影响。完整雄性大鼠循环中LH和T的迅速而显著升高表明内源性雄激素的负反馈作用得到有效拮抗，提示F可作为垂体-睾丸功能激发试验。垂体对促性腺激素释放激素（LHRH）的反应明显增强，如先前在去势大鼠中所发现的。F的给药对经T处理或未经处理的去势大鼠的循环T水平没有影响，表明循环中的F对T测定没有干扰。得出的结论是，与甾体类抗雄激素环丙孕酮一样，非甾体类的F一方面对周围雄激素依赖性和中枢反馈机制的作用，与另一方面对性行为的作用之间存在差异。F治疗后射精行为的抑制是中枢介导的，还是由于周围雄激素依赖性结构或功能元件的失效导致的，尚未确定。
