Effects of endogenous sex hormones on mouse liver ethylmorphine N-demethylase.
For most commonly used mouse strains there is either no sex difference in drug metabolism, or females have a higher rate of metabolism than males of the same strain. In the CRL:CD-1 strain, for example, the males have a lower Vmax and a higher Km than females for ethylmorphine N-demethylation. By contrast, kinetic analysis for this pathway of drug metabolism in the BALB/cJ mouse strain demonstrated that males have a higher Vmax and a lower Km than females. Although gonadal hormones appear to play a similar role in both the strains with respect to body weight, liver weight, microsomal protein content, and the weights of sex hormone responsive organs, a strict dependence of the sex differences in ethylmorphine (EM) metabolism on gonadal hormones could not be demonstrated. A systematic analysis of the spectral interactions of EM with cytochrome P-450 (P-450), the activities of NADPH P-450 reductase and NADPH oxidase in these mouse strains did not reveal a common regulatory site for gonadal hormones. Moreover, sex differences in EM N-demethylase activity are not a direct function of the total P-450 present in hepatic microsomes since, for both strains, males have higher P-450 content than females. We conclude, therefore, that sex differences in hepatic EM N-demethylase activity in the BALB/cJ and CRL:DC-1 mouse strains may depend on the relative quantities of the individual forms of microsomal P-450 which appear to be under genetic and/or hormonal control.
D000818:Animals; D002369:Castration; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005037:Ethylmorphine-N-Demethylase / Q000378:metabolism*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism
D012739:Gonadal Steroid Hormones; D011506:Proteins; D003577:Cytochrome P-450 Enzyme System; D010089:Oxidoreductases, N-Demethylating; D005037:Ethylmorphine-N-Demethylase