Gustafsson J A, Ingelman-Sundberg M, Stenberg A, Neumann F
J Endocrinol. 1975 Feb;64(2):267-75. doi: 10.1677/joe.0.0640267.
The metabolism of (4-14C)4-androstene-3,17-dione, (4-14C)5alpha-androstane-3alpha, 17beta-diol and (1,2-3H)5alpha-androstane-3alpha, 17beta-diol 3,17-disulphate was studied using the microsomal fraction and the metabolism of (4-14C)4-androstene-3,17-dione was studied using the 105 000 g supernatant fraction of liver from male and female rats aged 5 months that had been treated with cyproterone acetate before (from day 13 of pregnancy) and after birth (until 3 weeks of age). Nearly all sex-dependent enzyme activities in the treated male rats were changes in a direction characteristic of female rats: 5alpha-reductase active on 4-androstene-3,17-dione increased in activity whereas 3beta- and 17alpha-hydroxysteroid reductases and 6beta- and 16alpha-hydroxylases active on 4-androstene-3,17-dione and 2alpha-, 2beta- and 18-hydroxylases active on 5alpha-androstane-3alpha,17beta-diol decreased in activity. Enzyme activities not under gonadal control, i.e. 3alpha- and 17beta-hydroxysteroid reductases active on 4-androstene-3,17-dione and 7alpha-hydroxylase active on both 4-androstene-3,17-dione and 5alpha-androstane-3alpha, 17beta-diol, were not affected by cyproterone acetate. The liver enzyme activities in treated female rate were generally not affected although significant effects were noted in two cases; in one of these (17alpha-hydroxysteroid reductase) a testosterone-like effect was observed. The results obtained are probably best explained in the following way: treatment with theanti-androgen during the neonatal period results in less efficient imprinting of the hypothalamo-hypophysial system leading to less pronounced masculine setting of sex-dependent enzyme levels and also to a relative androgen unresponsiveness. It is suggested that the biochemical methods used in the degree of neonatal sexual differentiation of the hypothalamo-hypophysial system than biological and psychological methods previously available.
研究了（4-¹⁴C）4-雄烯-3,17-二酮、（4-¹⁴C）5α-雄烷-3α,17β-二醇和（1,2-³H）5α-雄烷-3α,17β-二醇3,17-二硫酸盐的微粒体代谢，并研究了（4-¹⁴C）4-雄烯-3,17-二酮在5个月龄雄性和雌性大鼠肝脏105 000g上清液中的代谢，这些大鼠在妊娠第13天之前和出生后（直至3周龄）用醋酸环丙孕酮处理过。在经处理的雄性大鼠中，几乎所有性别依赖性酶活性都朝着雌性大鼠特有的方向变化：作用于4-雄烯-3,17-二酮的5α-还原酶活性增加，而作用于4-雄烯-3,17-二酮的3β-和17α-羟基类固醇还原酶以及6β-和16α-羟化酶，以及作用于5α-雄烷-3α,17β-二醇的2α-、2β-和18-羟化酶活性降低。不受性腺控制的酶活性，即作用于4-雄烯-3,17-二酮的3α-和17β-羟基类固醇还原酶以及作用于4-雄烯-3,17-二酮和5α-雄烷-3α,17β-二醇的7α-羟化酶，不受醋酸环丙孕酮影响。经处理的雌性大鼠肝脏酶活性一般不受影响，尽管在两个案例中观察到显著影响；其中一个案例（17α-羟基类固醇还原酶）观察到类似睾酮的效应。所获得的结果可能最好用以下方式解释：在新生儿期用抗雄激素治疗会导致下丘脑-垂体系统的印记效率降低，导致性别依赖性酶水平的男性化特征不明显，并且还导致相对雄激素无反应性。有人提出，与以前可用的生物学和心理学方法相比，这里使用的生化方法在评估下丘脑-垂体系统新生儿性别分化程度方面更敏感。
