Danazol inhibits steroidogenesis in the rat testis in vitro.
Danazol inhibits steroidogenesis in the rat testis in vitro.
复制标题
达那唑在体外抑制大鼠睾丸中的类固醇生成。
DOI：
10.1210/endo-101-6-1676
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发表时间：
1977
期刊：
影响因子：
4.8
通讯作者：
K. Ryan
中科院分区：
文献类型：
--
作者：
R. Barbieri;J. Canick;K. Ryan
通过研究达那唑对大鼠睾丸体外类固醇生成的影响：1）用达那唑培养的大鼠Leydig细胞中雄激素的合成，2）达那唑与大鼠睾丸微粒体细胞色素P-450的结合，3）达那唑抑制睾丸类固醇生成微粒体酶的酶动力学。浓度低至1微米的达那唑抑制LH刺激的睾丸激素和雄烯二酮在培养的Leydig细胞的生产。向睾丸微粒体制剂中加入达那唑引起I型细胞色素P-450结合光谱，表观光谱解离常数（Ks）为4.8 μ m。达那唑抑制孕酮和17 α-羟孕酮与微粒体P-450的结合，其表观光谱抑制常数分别为2.4 μ m和2.8 μ m。达那唑竞争性抑制3 β-羟基-δ 5-类固醇脱氢酶-异构酶（表观酶抑制常数，KI = 5.8微米）、17 α-羟化酶（KI = 2.4微米）、17，20裂解酶（KI = 1.9微米）和17 β-羟基类固醇脱氢酶（KI = 4.4微米）。这些结果表明，低浓度的达那唑直接抑制类固醇激素在大鼠睾丸在体外。
The effects of danazol on steroidogenesis in vitro in the rat testis were examined by studying: 1) androgen synthesis in rat Leydig cells cultured with danazol, 2) danazol binding to rat testis microsomal cytochrome P-450, and 3) enzyme kinetics of danazol inhibition of the microsomal enzymes of testicular steroidogenesis. Concentrations of danazol as low as 1 micrometer suppressed LH-stimulated testosterone and androstenedione production in cultured Leydig cells. The addition of danazol to a preparation of testicular microsomes elicited a type I cytochrome P-450 binding spectrum, with an apparent spectral dissociation constant (Ks) of 4.8 micrometer. Danazol inhibited progesterone and 17alpha-hydroxy-progesterone binding to microsomal P-450 with apparent spectral inhibition constants of 2.4 micrometer and 2.8 micrometer, respectively. Danazol competitively inhibited 3beta-hydroxy-delta5-steroid dehydrogenase-isomerase (apparent enzymatic inhibition constant, KI = 5.8 micrometer), 17alpha-hydroxylase (KI = 2.4 micrometer), 17,20 lyase (KI = 1.9 micrometer), and 17beta-hydroxysteroid dehydrogenase (KI = 4.4 micrometer). These findings indicate that low concentrations of danazol directly inhibit steroidogenesis in the rat testis in vitro.