Malozowski S, Young I, Garcia H, Simoni C, Loriaux D L, Cassorla F
Steroids. 1985 Jul;46(1):659-63. doi: 10.1016/0039-128x(85)90029-7.
Ketoconazole (K) is an antifungal imidazole derivative which has been shown to be a potent inhibitor of testosterone (T) biosynthesis in rodents and humans. To study the effect of K on rat testicular steroidogenesis we measured the activities of five testicular microsomal steroidogenic enzymes in K-treated rats and controls. Thirty male adult rats were given either 2 mg K or water every 12 hours by mouth during 5 days. Mean testicular weight was similar in both groups of animals. The K-treated group had a T serum concentration of 83 +/- 14 ng/dL whereas it was 94 +/- 16 ng/dL in the control group (NS). The K-treated animals had decreased activities of the 3 beta-hydroxysteroid dehydrogenase (830 +/- 48 vs 2,245 +/- 109 pmol/mg protein/min, P less than 0.001), 17-hydroxylase (243 +/- 5 vs 676 +/- 17 pmol/mg protein/min, P less than 0.001), 17-ketosteroid reductase (31 +/- 2 vs 169 +/- 7 pmol/mg protein/min, P less than 0.001), and aromatase enzymes (92 +/- 6 vs 123 +/- 7 pmol/mg protein/min, P less than 0.01). The 17,20-desmolase activity was similar in both groups of animals (210 +/- 4 vs 171 +/- 18 pmol/mg protein/min). We conclude that K given orally to rats inhibits the activity of several testicular steroidogenic enzymes.
酮康唑（K）是一种抗真菌咪唑衍生物，已被证明是啮齿动物和人类睾酮（T）生物合成的有效抑制剂。为了研究K对大鼠睾丸类固醇生成的影响，我们测量了K处理组大鼠和对照组大鼠睾丸中五种微粒体类固醇生成酶的活性。30只成年雄性大鼠在5天内每12小时经口给予2mg K或水。两组动物的平均睾丸重量相似。K处理组的血清T浓度为83±14ng/dL，而对照组为94±16ng/dL（无显著性差异）。K处理的动物中，3β-羟基类固醇脱氢酶活性降低（830±48对2245±109pmol/mg蛋白质/分钟，P<0.001），17-羟化酶活性降低（243±5对676±17pmol/mg蛋白质/分钟，P<0.001），17-酮类固醇还原酶活性降低（31±2对169±7pmol/mg蛋白质/分钟，P<0.001），芳香化酶活性降低（92±6对123±7pmol/mg蛋白质/分钟，P<0.01）。两组动物的17,20-裂解酶活性相似（210±4对171±18pmol/mg蛋白质/分钟）。我们得出结论，经口给予大鼠K可抑制几种睾丸类固醇生成酶的活性。
