Sex Hormone-Related Control of Hepatic Epoxide Hydrolase Activities in Mice.

Abstract

Sex-related differences in hepatic epoxide hydrolase (EH) activities towards 7-(2',3'-epoxy)propoxycoumarin (7-glycidoxycoumarin, GOC) were investigated, mainly in mice but also in rats. Hepatic subcellular EH activities in the ddY mouse were higher in microsomes than in the soluble and mitochondrial fractions and sex-related differences were noted in all the subcellular fractions where males had significantly higher activities than females. Sex differences in the hepatic microsomal and soluble activities similar to those in the ddY strain were also observed in two other strains of mice, A/J and C3H/He, and in Wistar rats. In the ddY strain, castration of the males caused decreases in microsomal and soluble EH activities, while no alteration in the activities in those fractions was found following castration of females. Treatment of the male castrates with testosterone led to recovery of the activities in microsomal and soluble fractions while hormone treatment of female castrates caused a rise only in microsomal activity. Estradiol treatments of both sexes did not cause any changes in the hepatic subcellular activities. In intact ddY mice, testosterone treatment did not affect the male microsomal and soluble EH activities, but resulted in stimulation of both subcellular enzyme activities in females. In contrast, estradiol treatment showed a suppressive effect on both subcellular activities in males, but had no effect on female activities. These results show that hepatic EH activities towards GOC are mainly under androgenic stimulatory control in mice.