Administration of testosterone alleviates the constitutive sex difference in rat brain cytochrome P-450

Abstract

Sex-related difference was observed in the levels of total cytochrome P-450 (P-450) and the mono-oxygenase activity mediated by P-450(b,e), namely, aminopyrine N-demethylase and morphine N-demethylase activity in rat brain microsomes. Male rat brain had higher activity of the above enzymes as compared to the female rat brain. On the other hand, P-450_(c,d) mediated 7-ethoxycoumarin O-deethylase and benzo(a)pyrene hydroxylase activity showed no sex-related difference in rat brain. Administration of testosterone elevated the levels of total P-450, aminopyrine N-demethylase and morphine N-demethylase in female rat brain to levels comparable with that of the male rat brain. No significant change was observed in the levels of 7-ethoxycoumarin O-deethylase and benzo(a)pyrene hydroxylase and NADPH cytochrome c reductase. All of the above enzyme levels were unaffected in the male rat brain following the treatment with testosterone. These results indicate that testosterone may regulate the forms of cerebral P-450 that are associated with the sex-related difference observed in rat brain.