男性胎儿5α-还原酶活性和雄激素及其受体的研究

Steroid 5α-Reductase Activity, Androgen Level and Its Receptor in the Target Tissues of Male Fetuses

目的 :分析男性胎儿雄激素靶组织外生殖器皮肤的雄激素 (T、DHT)水平、5α 还原酶活性及雄激素受体(AR)配基结合能力 ,探讨其在性别分化成熟中的作用。 方法 :4例孕 16～ 2 0周因意外事件而被迫引产的胎儿 ,取其包皮和阴茎皮肤组织。 10例 4～ 7岁和 2 3例 2 0～ 3 4岁男性因包茎或包皮过长行包皮环切术后的组织 ,制备匀浆 ,经差速超速离心 ,分别制备胞质、核浆和微粒体 3种组份 ,RIA方法测定匀浆中T、DHT水平 ,按作者建立和改良的方法分析 5α 还原酶活性及雄激素受体 (AR)配基结合能力 (B)。 结果 :孕 16～ 2 0周男性胎儿靶组织T为 ( 4 .5 5± 2 .84 )pmol/(mg蛋白·ml) ,DHT为 ( 3 9.12± 17.3 0 )pmol/(mg蛋白·ml) ;5α 还原酶 Ⅰ 型同工酶活性为 ( 162 .15±3 6.94 )pmol/(mg蛋白·3 0min) ,Ⅱ 型同工酶活性为 ( 3 0 7.62± 4 0 .5 5 )pmol/(mg蛋白·3 0min) ;胞质AR的B值为 ( 18.86± 7.62 )fmol/mg蛋白 ,核内AR的B值为 ( 10 8.5 5± 4 9.3 4 )fmol/mg蛋白。各项参数均高于儿童时期 ;除AR外 ,甚至高于成年男子 (P <0 .0 5～ 0 .0 1)。 结论 :胎儿时期雄激素靶组织中具有高水平的雄激素及其受体 ,尤其DHT ,提示雄激素在介导男性外生殖器分化形成和成熟中起重要的调控作用。

Objectives: To measure the 5α-reductase activity, androgen (testosterone and dihydrotestosterone, T and DHT) levels and the ligand binding capacity of androgen receptor (AR) in the androgen target tissues-genital skin of male fetuses, and evaluate the effect of androgen on the sexual differentiation and development. Methods: Four samples of foreskins were acquired from four male fetuses with consent at the pregnancy age of 16～20 weeks who had been aborted due to emergency accident. As control, the foreskins were obtained from 10 male children aged 4 to 7 ys and 23 adult men aged 20 to 34 ys when circumcision due to phimosis. T and DHT levels were measured with the method of RIA. 5α-reductase activity and AR binding capacity were assayed with the methods developed in our laboratory. Results: In male fetuses, T level in target tissues was (4.55±2.84)pmol/(mg protein·ml), DHT (39.12±17.30) pmol/(mg protein·ml); 5α-reductase type Ⅰ activity (162.15±36.94)pmol/(mg protein·30min), type Ⅱ (307.62±40.55)pmol/(mg protein·30min); the ligant binding capacity of cytosole AR (18.86±7.62)fmol/mg protein, nuclear AR (108.55±49.34) fmol/mg protein. These data were higher than those in male children and adult men (P<0.05～0.01), except for AR capacity. Conclusions: Androgen and AR, as well as 5α-reductase, were at the high status in male fetuses, suggesting that androgen, especially DHT, played an important role in regulating the sexual differentiation and development.