Abstract

Expression of microsomal epoxide hydrolase (mEH), levels of mEH mRNA, and the rate of mEH mRNA transcription were examined in hepatic and renal tissues at 4, 24, 44, and 56 weeks of age in male and 4, 14, 24, 34, and 44 weeks of age in female Sprague-Dawley rats. Immunoblot analyses revealed that hepatic mEH levels in males increased in an age-dependent manner, with a maximal increase (approximately 3-fold) being noted at 44 weeks of age, whereas the expression of hepatic mEH in females decreased significantly at 14 weeks of age or older, by approximately 70%s, compared with that of 4-week-old rats. Microsomes from kidney tissue failed to exhibit an age-dependent change in either sex. mEH mRNA levels were measured in total and poly(A)+ RNA isolated from hepatic and renal tissues. RNA blot hybridization analyses, probed with a 1.3-kilobase mEH cDNA, revealed that the levels of hepatic mEH mRNA in total RNA isolated from males were elevated approximately 1.5-, 2.8-, and 2.3-fold at 24, 44, and 56 weeks of age, respectively, relative to those at 4 weeks of age, whereas the levels of hepatic mEH mRNA in poly(A)+ RNA from males failed to change in an age-dependent manner. In contrast, the levels of hepatic mEH mRNA in either total or poly(A)+ RNA from female animals were dramatically decreased from 4 to 14 weeks of age, by approximately 90%. The suppressed levels of mEH mRNA in females were maintained at 24, 34, and 44 weeks of age (approximately 80%). However, the levels of renal mEH mRNA failed to change in an age-dependent manner in either sex, which was consistent with there being no change in the levels of mEH protein in kidney. In order to examine whether the gender-related maturational changes in hepatic mEH mRNA levels could result from transcriptional regulation, nuclear run-on assays were performed. The rate of hepatic mEH gene transcription failed to change in either males or females at the ages that exhibited significant changes in both mRNA levels and protein expression, suggesting that transcriptional regulation is not associated with the gender-dependent modulation of mEH mRNA levels during maturation.(ABSTRACT TRUNCATED AT 400 WORDS)