Sex differences in cytochrome P-450 isozyme composition and activity in kidney microsomes of mature rainbow trout.
Sex differences in cytochrome P-450 isozyme composition and activity in kidney microsomes of mature rainbow trout.
复制标题
成熟虹鳟鱼肾微粒体细胞色素 P-450 同工酶组成和活性的性别差异。
DOI：
10.1016/0006-2952(86)90735-5
复制
发表时间：
1986
影响因子：
5.8
通讯作者：
Buhler,DR
中科院分区：
文献类型：
--
作者：
Williams,DE;Masters,BS;Lech,JJ;Buhler,DR
与雌性虹鳟鱼相比，性成熟雄性虹鳟鱼的肾微粒体的细胞色素 P-450 特异性含量、NADPH-细胞色素还原酶活性以及月桂酸、睾酮、孕酮和黄曲霉毒素 B1 的羟基化率高出约 20 倍。以苯并[a]芘或苯异丙胺作为底物，观察到代谢中很少或没有性别差异。在这些鱼的肝微粒体中也观察到了类似的模式，但差异不太明显（雄性的活性高出大约 2 倍）。幼年鳟鱼（两性）的活动介于成熟雄性和雌性之间。幼年和性成熟雄性和雌性鳟鱼肾脏和肝脏微粒体的十二烷基硫酸钠聚丙烯酰胺凝胶电泳表明，肾脏中显着的性别差异可能是由于性成熟雄性鳟鱼P-450同工酶LM2含量较高所致。通过蛋白质印迹法和兔抗鳟鱼 LM2-IgG 免疫染色对 LM2 进行免疫定量，证实成熟雄性肾脏中 P-450 LM2 的水平远高于幼年或雌性肾脏，甚至三组的肝微粒体。成熟雌性肾微粒体中 P-450 LM2 的含量几乎检测不到。雄性鳟鱼肾脏中的高含量 LM2 与这些微粒体对月桂酸和黄曲霉毒素 B1 的高活性一致，先前已表明这些物质优先被鳟鱼 P-450 LM2 代谢。建议虹鳟鱼可以作为大鼠的替代动物模型，用于研究细胞色素 P-450 的性别依赖性差异。
Kidney microsomes from sexually mature male, as opposed to female, rainbow trout displayed an approximately 20-fold higher cytochrome P-450 specific content, NADPH-cytochromecreductase activity, and rates of hydroxylation of lauric acid, testosterone, progesterone and aflatoxin B1. Little or no sex difference in metabolism was observed with benzo[a]pyrene or benzphetamine as substrates. A similar pattern was observed in hepatic microsomes from these fish, but the difference was much less striking (approximately 2-fold higher activity in males). Juvenile trout (both sexes) possessed activities intermediate between mature males and females. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of kidney and liver microsomes of juvenile and sexually mature male and female trout suggested that the striking sex difference in kidney could be due to the high amount of trout P-450 isozyme LM2in sexually mature males. Immunoquantitation of LM2, performed by Western Blotting and immunostaining with rabbit anti-trout LM2-IgG, confirmed that mature male kidney contained much higher levels of P-450 LM2than juvenile or female kidney, or even of liver microsomes of all three groups. The amount of P-450 LM2in mature female kidney microsomes was barely detectable. The high amount of LM2in male trout kidney is consistent with the high activity of these microsomes towards lauric acid and aflatoxin B1, which have been shown previously to be preferentially metabolized by trout P-450 LM2. It is suggested that rainbow trout may serve as an alternative to the rat as an animal model for the study of sex-dependent differences in cytochromes P-450.