Hormonal regulation of the developmental pattern of epoxide hydrolases. Studies in rat liver

Hormonal influences on the developmental pattern of epoxide hydrolases (EH) were investigated in livers from male and female Fischer F-344 rats. During ontogeny, activities of rat liver microsomal and cytosolic epoxide hydrolases (cEH and mEH) increased gradually until puberty when activities in males rose rapidly to become 1.5-fold to 2.0-fold higher than those in females. These sex differences were not observed in the adult rat if males were castrated 24 hr after birth. In castrated males, as well as in females, testosterone propionate (TP, 0.5 mg s.c. in 50 microliters peanut oil) injected on days 1, 3 and 5 postpartum increased mEH and cEH activities at adulthood compared to peanut oil-treated controls. In another study to determine effects on adults of neonatal exposure to a prototype-inducing agent, phenobarbital (PB, 30 mg/kg s.c., qd, in 0.9% saline) was injected in male and female neonates on days 1 through 5 postpartum. Although no long-term effect on mEH activities appeared on days 28, 45 and 60, hepatic mEH activities increased in all treatment groups on days 90 and 120. Collectively, these studies indicate that neonatal exposure to testosterone and PB alters the developmental pattern of EH activities, including final adult levels. Thus, full adult expression of these activities depends on hormonal influences exerted neonatally.