Ayub M, Levell M J
J Steroid Biochem. 1987 Jul;28(1):43-7. doi: 10.1016/0022-4731(87)90122-1.
Flutamide, hydroxyflutamide, RU23908 and cyproterone acetate (CPA) inhibited rat testicular microsomal 17 alpha-hydroxylase and 17,20-lyase activities in vitro. The Km of [3H] progesterone for 17 alpha-hydroxylase was 45 +/- 0.62 nmol/l (+/- SEM, n = 12) and the Km of [3H] 17 alpha-hydroxyprogesterone for 17,20-lyase was 192 +/- 0.42 nmol/l (+/- SEM, n = 12). The Ki values for 17 alpha-hydroxylase, determined from Lineweaver-Burk plots were 102 +/- 3.2 mumol/l (+/- SEM, n = 6), 363 +/- 3.8 mumol/l (+/- SEM, n = 6), 118 +/- 1.4 mumol/l (+/- SEM, n = 6) and 123 +/- 2.1 mumol/l (+/- SEM, n = 6) for flutamide, hydroxyflutamide, RU23908 and CPA respectively. Flutamide and CPA were mixed-type inhibitors, whereas hydroxyflutamide and RU23908 were competitive inhibitors of 17 alpha-hydroxylase activity. Ki values for 17,20-lyase were 33 +/- 3.1 mumol/l (+/- SEM, n = 6), 112 +/- 3.1 mumol/l (+/- SEM, n = 6), 69 +/- 4.4 mumol/l (+/- SEM, n = 6) and 71 +/- 3.2 mumol/l (+/- SEM, n = 6) for flutamide, hydroxyflutamide, RU23908 and CPA, respectively. Inhibition was found to be competitive in each case. Although the characteristic action of anti-androgens is at the receptor level, these results demonstrate that anti-androgens may also have inhibitory effects on androgen biosynthesis which could prove to be of clinical significance.
氟他胺、羟基氟他胺、RU23908和醋酸环丙孕酮（CPA）在体外抑制大鼠睾丸微粒体17α-羟化酶和17,20-裂解酶活性。17α-羟化酶对[3H]孕酮的Km为45±0.62nmol/L（±标准误，n = 12），17,20-裂解酶对[3H]17α-羟孕酮的Km为192±0.42nmol/L（±标准误，n = 12）。根据Lineweaver-Burk图确定的氟他胺、羟基氟他胺、RU23908和CPA对17α-羟化酶的Ki值分别为102±3.2μmol/L（±标准误，n = 6）、363±3.8μmol/L（±标准误，n = 6）、118±1.4μmol/L（±标准误，n = 6）和123±2.1μmol/L（±标准误，n = 6）。氟他胺和CPA为混合型抑制剂，而羟基氟他胺和RU23908是17α-羟化酶活性的竞争性抑制剂。氟他胺、羟基氟他胺、RU23908和CPA对17,20-裂解酶的Ki值分别为33±3.1μmol/L（±标准误，n = 6）、112±3.1μmol/L（±标准误，n = 6）、69±4.4μmol/L（±标准误，n = 6）和71±3.2μmol/L（±标准误，n = 6）。在每种情况下均发现抑制作用具有竞争性。尽管抗雄激素的特征性作用是在受体水平，但这些结果表明抗雄激素也可能对雄激素生物合成具有抑制作用，这可能具有临床意义。
