Pinot F, Grant D F, Spearow J L, Parker A G, Hammock B D
Department of Entomology, University of California, Davis 95616-8584, USA.
Biochem Pharmacol. 1995 Aug 8;50(4):501-8. doi: 10.1016/0006-2952(95)00167-x.
Soluble epoxide hydrolase (sEH) activity was measured in the liver and kidneys of male, female, and castrated male mice in order to evaluate sex- and tissue-specific differences in enzyme expression. sEH activity was found to be higher in liver than in kidneys. Activity increased with age in the liver of females, males and castrated males, but only in males did activity in the kidneys increase. There was greater activity in both the liver and kidneys of adult males than females. This sexual dimorphism was more pronounced in the kidneys (283% higher) than in the liver (55% higher). Castration of males led to a decrease in activity in both organs, but it had a greater effect on renal activity (67% decrease) than on hepatic activity (27% decrease). Treatment of castrated mice with testosterone led to an increase in sEH activity of 400% in kidneys and 49% in liver compared with surgical controls. These results suggest differential regulation of sEH by testosterone in kidneys and liver. Ovariectomized female mice had renal and hepatic activities approximately 30% greater than control females. Feeding mice with the hypolipidemic drug clofibrate produced stronger induction of sEH in liver than in kidneys. Testosterone treatment, however, caused greater induction in kidneys than in liver of females and castrated males and had no effect in either kidneys or liver in males. When given together, the effects of these two compounds appeared to be additive in both liver and kidneys. Results from western blot showed that the increase in sEH enzyme activity in kidneys is correlated with an increase in sEH protein. These results suggest that clofibrate and testosterone independently regulate sEH activity in vivo, and that kidneys and liver respond differently to clofibrate and testosterone.
为了评估可溶性环氧化物水解酶（sEH）在酶表达方面的性别和组织特异性差异，我们测定了雄性、雌性和去势雄性小鼠肝脏和肾脏中的sEH活性。结果发现，肝脏中的sEH活性高于肾脏。雌性、雄性和去势雄性小鼠肝脏中的活性随年龄增加而升高，但仅雄性小鼠肾脏中的活性增加。成年雄性小鼠肝脏和肾脏中的活性均高于雌性。这种性别二态性在肾脏中（高283%）比在肝脏中（高55%）更为明显。雄性去势导致两个器官的活性均降低，但对肾脏活性的影响（降低67%）大于对肝脏活性的影响（降低27%）。与手术对照组相比，用睾酮治疗去势小鼠可使肾脏中的sEH活性增加400%，肝脏中的增加49%。这些结果表明，睾酮对肾脏和肝脏中sEH的调节存在差异。卵巢切除的雌性小鼠肾脏和肝脏的活性比对照雌性小鼠高约30%。给小鼠喂食降血脂药物氯贝丁酯对肝脏中sEH的诱导作用比对肾脏更强。然而，睾酮治疗对雌性和去势雄性小鼠肾脏的诱导作用比对肝脏更强，对雄性小鼠的肾脏和肝脏均无影响。当两种化合物同时使用时，它们在肝脏和肾脏中的作用似乎是相加的。蛋白质免疫印迹结果显示，肾脏中sEH酶活性的增加与sEH蛋白的增加相关。这些结果表明，氯贝丁酯和睾酮在体内独立调节sEH活性，并且肾脏和肝脏对氯贝丁酯和睾酮的反应不同。
