Male-female differences in ethylmorphine N-demethylase activity and cytochrome P-450 content were studied in BALB/cJ, DBA/2J, C3H/HeJ, C57BL/10J and CRL:CD-1 mouse strains. Demethylase activity was greater for male mice than females of the BALB/cJ strain, but the inverse male-female relationship existed for CRL:CD-1 mice. No consistent sex differences were present in the other strains. However, hepatic microsomal cytochrome P-450 content was greater in male mice of all strains studied. The effect of testosterone administration (1, 2 or 5 mg/day, 6 days, s.c.) was investigated in intact female mice of each strain. BALB/cJ mice demonstrated a dose-dependent increase in body and liver weights, whereas all five strains displayed increased microsomal protein content in response to the administration of testosterone. Testosterone produced a dose-related increase in ethylmorphine N-demethylase activity and cytochrome P-450 content of BALB/cJ mice. An increase in cytochrome P-450 content of C3H/HeJ mice was the only other response observed following testosterone treatment. These observations support the following conclusions: only certain mouse strains demonstrate a sex difference in ethylmorphine N-demethylase activity and in those strains males may have higher or lower activity than females; sex differences in cytochrome P-450 content are not accompanied by predictable differences in demethylase activity; testosterone stimulation of hepatic microsomal protein content represents one type of androgen action whereas effects on demethylase activity and cytochrome P-450 content represent another; and hepatic microsomal N-demethylase activity is under genetic control such that androgen effects on this activity in adult mice are strain-specific.
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