Parker A G, Pinot F, Grant D F, Spearow J, Hammock B D
Department of Entomology and Environmental Toxicology, University of California, Davis 95616-8584, USA.
Biochem Pharmacol. 1996 Mar 8;51(5):677-85. doi: 10.1016/s0006-2952(95)02254-6.
Carboxylesterase activity was measured using six different substrates in microsomal preparations from female and ovariectomized female mice in order to evaluate the effects of female sex hormones on esterase expression. With three of the substrates (alpha-naphthyl acetate and esters 2 and 3), esterase activity was the same in both groups; however, with the others (rho-nitrophenyl acetate and esters 1 and 4), there was a small increase in activity in ovariectomized females, compared with intact females. Castration of males followed by treatment with testosterone caused only transient increases in activity for four of the substrates (alpha-naphthyl acetate and esters 1, 2, and 3) and no change in activity for the other two (rho-nitrophenyl acetate and ester 4). Treatment of male and female mice with the peroxisome proliferator clofibrate, with or without testosterone, resulted in increased hydrolysis of alpha-naphthyl acetate and rho-nitrophenyl acetate, but little change for the other substrates. Clofibrate also induced alpha-naphthyl acetate and rho-nitrophenyl acetate hydrolysis in castrated males, but clofibrate and testosterone administrated together resulted in significant increases of activity with all substrates, which were greater than the additive effects of the two compounds administered separately. These results indicate that clofibrate causes significant alterations in the regulation of esterase activity, whereas sex hormones only cause small changes. However, it would seem that testosterone can synergize the effect of clofibrate in castrated males, resulting in higher levels of activity than with clofibrate alone. Finally, an overall increase in esterase activity might be due to a large increase in the activity of a few esterases or to a small increase in many esterases. Enzyme staining of native polyacrylamide gels reveals that the latter is true, with the majority of esterases present in mouse liver microsomes being induced to a small degree by clofibrate.
为了评估雌性性激素对酯酶表达的影响，使用六种不同底物测量了雌性和去卵巢雌性小鼠微粒体制剂中的羧酸酯酶活性。对于其中三种底物（α-萘乙酸酯和酯2和3），两组的酯酶活性相同；然而，对于其他底物（对硝基苯乙酸酯和酯1和4），去卵巢雌性小鼠的活性与完整雌性小鼠相比有小幅增加。雄性阉割后用睾酮治疗，仅使四种底物（α-萘乙酸酯和酯1、2和3）的活性出现短暂增加，而另外两种底物（对硝基苯乙酸酯和酯4）的活性没有变化。用或不用睾酮处理雄性和雌性小鼠，过氧化物酶体增殖剂氯贝丁酯均导致α-萘乙酸酯和对硝基苯乙酸酯的水解增加，但其他底物变化不大。氯贝丁酯也诱导去势雄性小鼠的α-萘乙酸酯和对硝基苯乙酸酯水解，但氯贝丁酯和睾酮一起给药导致所有底物的活性显著增加，大于两种化合物单独给药的相加效应。这些结果表明，氯贝丁酯会导致酯酶活性调节发生显著改变，而性激素只会引起微小变化。然而，睾酮似乎可以增强氯贝丁酯对去势雄性小鼠的作用，导致活性水平高于单独使用氯贝丁酯时。最后，酯酶活性的总体增加可能是由于少数酯酶的活性大幅增加，或者是由于许多酯酶的活性小幅增加。天然聚丙烯酰胺凝胶的酶染色显示后者是正确的，小鼠肝脏微粒体中存在的大多数酯酶在一定程度上被氯贝丁酯诱导。
