Belham J E, Neal G E
Biochem J. 1971 Nov;125(1):81-91. doi: 10.1042/bj1250081.
Recent reports have indicated that the prior metabolism of testosterone by the secondary sexual tissues may be necessary for its androgenic effect. The effects of two anti-androgens, diethylstilboestrol and cyproterone acetate (17alpha-acetoxy-6-chloro-1,2alpha-methylenepregna-4,6-diene-3,20-dione) used in the chemotherapy of human prostatic carcinoma, have been examined on both the metabolism of testosterone and the retention of its metabolites by the rat ventral prostate gland. Cyproterone acetate was found to inhibit the retention of labelled metabolites of [(3)H]-testosterone by prostatic nuclei, both in vivo and in vitro. This inhibition appeared to be competitive. In contrast with its effect on nuclear retention of metabolites of testosterone, cyproterone acetate had no significant effect on the metabolism of [(3)H]testosterone by rat ventral prostate tissue. Diethylstilboestrol similarly had little effect on the metabolism of [(3)H]testosterone by prostatic tissue, although it did appear partially to inhibit its initial metabolism in all the incubation systems used. Diethylstilboestrol inhibited the nuclear retention of dihydrotestosterone when both [(3)H]testosterone and diethylstilboestrol were injected intraperitoneally in vivo, but had no effect on dihydrotestosterone retention when both testosterone and diethylstilboestrol were supplied directly to the prostate either in vivo or in vitro. It was concluded that if diethylstilboestrol has an anti-androgenic effect at the level of the target organ as distinct from its effect on androgen production by the testes, then it is probably due to a mechanism differing from that of cyproterone acetate.
最近的报告表明，睾酮在第二性征组织中的前期代谢可能是其雄激素效应所必需的。已研究了两种用于人类前列腺癌化疗的抗雄激素药物，己烯雌酚和醋酸环丙孕酮（17α-乙酰氧基-6-氯-1,2α-亚甲基孕甾-4,6-二烯-3,20-二酮）对睾酮代谢以及大鼠腹侧前列腺对其代谢产物的潴留的影响。发现醋酸环丙孕酮在体内和体外均能抑制前列腺细胞核对[³H] - 睾酮标记代谢产物的潴留。这种抑制作用似乎是竞争性的。与它对睾酮代谢产物核潴留的影响相反，醋酸环丙孕酮对大鼠腹侧前列腺组织对[³H]睾酮的代谢没有显著影响。己烯雌酚对前列腺组织对[³H]睾酮的代谢同样影响很小，尽管在所有使用的孵育系统中它似乎确实部分抑制了其初始代谢。当在体内腹腔注射[³H]睾酮和己烯雌酚时，己烯雌酚抑制二氢睾酮的核潴留，但当在体内或体外将睾酮和己烯雌酚直接提供给前列腺时，它对二氢睾酮的潴留没有影响。得出的结论是，如果己烯雌酚在靶器官水平具有抗雄激素作用，与其对睾丸雄激素产生的影响不同，那么其机制可能与醋酸环丙孕酮不同。
