In Vitro inhibition by ketoconazole of human testicular steroid oxidoreductases

Journal of steroid biochemistry Pub Date : 1990-08-28 DOI:10.1016/0022-4731(90)90186-V

Yotsuo Higashi, Ken-Ichiro Yoshida , Hiroyuki Oshima

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引用次数: 5

Abstract

An oral antimycotic agent, ketoconazole has been demonstrated to be an inhibitor of cytochrome P-450-dependent monooxygenases. To investigate its effect on steroid oxido-reductases, in vitro studies were carried out using subcellular fractions of human testes. Ketoconazole competitively inhibited activities of 3β-hydroxy-5-ene-steroid oxidoreductase/ isomerase and NADH-linked 20α-hydroxysteroid oxidoreductase for steroid substrate and the K_i values were 2.9 and 0.9 μM, respectively. In contrast, ketoconazole inhibited neither 17β-hydroxysteroid oxidoreductase nor NADPH-linked 20α-hydroxysteroid oxido-reductase, indicating that the two 20α-hydroxysteroid oxidoreductases are distinct. Further, ketoconazole inhibited non-competitively the above enzyme activities for the corresponding cofactors of NAD and NADH. From the binding mode of ketoconazole to cytochrome P-450 and the present findings, it appears likely that the agent binds to a site which is different from that of steroids or pyridine nucleotides.

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酮康唑对人睾丸类固醇氧化还原酶的体外抑制作用

酮康唑是一种口服抗真菌剂，已被证明是细胞色素p -450依赖性单加氧酶的抑制剂。为了研究其对类固醇氧化还原酶的影响，使用人睾丸的亚细胞部分进行了体外研究。酮康唑竞争性抑制3β-羟基-5-甾体氧化还原酶/异构酶和nadh连接的20α-羟基甾体氧化还原酶对甾体底物的活性，Ki值分别为2.9 μM和0.9 μM。相反，酮康唑对17β-羟基类固醇氧化还原酶和nadph连接的20α-羟基类固醇氧化还原酶均无抑制作用，说明这两种20α-羟基类固醇氧化还原酶是不同的。酮康唑对NAD和NADH相应辅因子的活性具有非竞争性抑制作用。从酮康唑与细胞色素P-450的结合方式和目前的发现来看，该药物结合的位点似乎与类固醇或吡啶核苷酸不同。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Journal of steroid biochemistry

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