司坦唑醇对猪睾丸细胞色素P-450（17α-羟化酶/C17,20-裂解酶）的抑制作用及相互作用

Inhibitory effect and interaction of stanozolol with pig testicular cytochrome P-450 (17 alpha-hydroxylase/C17,20-lyase).

作者信息

Nakajin S, Takahashi K, Shinoda M

出版信息

Chem Pharm Bull (Tokyo). 1989 Jul;37(7):1855-8. doi: 10.1248/cpb.37.1855.

DOI:10.1248/cpb.37.1855

Abstract

The inhibitory effect of an anabolic steroid, stanozolol, on testicular microsomal cytochrome P-450 (17 alpha-hydroxylase/C17,20-lyase) (P-450(17 alpha/lyase] and the nature of the interaction were compared with those of other anabolic steroids, furazabol and mestanolone. Stanozolol markedly inhibited delta 16-C19-steroid synthesizing activity, 17 alpha-hydroxylase and C17,20-lyase activities, which were mediated by oxygenase activities of testicular microsomal cytochrome P-450(17 alpha/lyase). In addition, stanozolol was a competitive inhibitor of 17 alpha-hydroxylase (Ki = 6.31 microM) and C17,20-lyase (Ki = 1.30 microM) activities in the reconstituted enzyme system. The interaction of cytochrome P-450&17 alpha/lyase) with stanozolol induced a type I difference spectrum (peak at 387 nm and trough at 418 nm) with a dissociation constant (Ks) of 1.47 microM.

摘要

将合成代谢类固醇司坦唑醇对睾丸微粒体细胞色素P-450（17α-羟化酶/C17,20-裂解酶）[P-450(17α/裂解酶)]的抑制作用及其相互作用的性质与其他合成代谢类固醇呋咱甲氢龙和美睾酮进行了比较。司坦唑醇显著抑制由睾丸微粒体细胞色素P-450(17α/裂解酶)的加氧酶活性介导的δ16-C19-类固醇合成活性、17α-羟化酶和C17,20-裂解酶活性。此外，在重组酶系统中，司坦唑醇是17α-羟化酶（Ki = 6.31 microM）和C17,20-裂解酶（Ki = 1.30 microM）活性的竞争性抑制剂。细胞色素P-450(17α/裂解酶)与司坦唑醇的相互作用诱导出I型差光谱（峰值在387 nm，谷值在418 nm），解离常数（Ks）为1.47 microM。