Duffy O, Berthou F, Bardou L G, Ménez J F
Laboratoire de Biochimie-Nutrition, Equipe d'accueil DRED, Faculté de Médecine, Brest, France.
Alcohol Alcohol. 1995 May;30(3):329-35.
Hydroxylation of testosterone (TST) has been shown to be regio- and stereo-specific for a number of cytochrome P-450 isoenzymes. Three rat lines [Sprague-Dawley (SpD), high alcohol sensitivity (HAS) and low alcohol sensitivity (LAS)] were tested for this enzymatic specificity after treatment with phenobarbital, clofibrate, 3-methylcholanthrene and pregnenolone-16 alpha-carbonitrile. These compounds are known to induce cytochrome P-450 2B, 4A, 1A and 3A1, respectively, in the rat. Induction efficiency was established by using the usual enzyme activities specific for these P-450s (pentoxyresorufin, lauric acid, ethoxyresorufin and nifedipine oxidase). Five mono hydroxylated TST metabolites were separated using a sensitive HPLC procedure. The hydroxylation of TST was found to be significantly different between the lines even in the uninduced state. The formation of the metabolites of TST, hydroxylated on 2 alpha or 7 alpha or 16 alpha positions and oxidated on carbon 17 (delta 4), was found to be significantly increased in SpD rats when compared with the HAS-LAS lines (P < 0.0001 in each case). When the HAS-LAS lines were compared, the quantity of 2 alpha and 16 alpha hydroxylated metabolites was found to be significantly lower in LAS rats (P < 0.05). These differences persisted, although in the opposite direction, after 3-methylcholanthrene (P < 0.01 for both 2 alpha and 16 alpha) and phenobarbital induction (P < 0.01 for 2 alpha).(ABSTRACT TRUNCATED AT 250 WORDS)
已证明，对于多种细胞色素P - 450同工酶，睾酮（TST）的羟基化具有区域和立体特异性。用苯巴比妥、氯贝丁酯、3 - 甲基胆蒽和孕烯醇酮 - 16α - 腈处理后，对三种大鼠品系[斯普拉格 - 道利（SpD）、高酒精敏感性（HAS）和低酒精敏感性（LAS）]进行了这种酶特异性测试。已知这些化合物分别在大鼠中诱导细胞色素P - 450 2B、4A、1A和3A1。通过使用这些P - 450特有的常规酶活性（戊氧基试卤灵、月桂酸、乙氧基试卤灵和硝苯地平氧化酶）来确定诱导效率。使用灵敏的高效液相色谱法分离了五种单羟基化的TST代谢物。即使在未诱导状态下，各品系间TST的羟基化也存在显著差异。与HAS - LAS品系相比，SpD大鼠中在2α或7α或16α位羟基化并在碳17（δ4）位氧化的TST代谢物的形成显著增加（每种情况P < 0.0001）。当比较HAS - LAS品系时，发现LAS大鼠中2α和16α羟基化代谢物的量显著较低（P < 0.05）。在3 - 甲基胆蒽诱导后（2α和16α均P < 0.01）和苯巴比妥诱导后（2α P < 0.01），这些差异仍然存在，尽管方向相反。（摘要截断于250字）
