Effects of endogenous sex hormones on mouse liver ethylmorphine N-demethylase

T. R. Brown, F. E. Greene

Research output: Contribution to journalArticlepeer-review

Abstract

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. It is concluded, therefore, that sex differences in hepatic EM N-demethylase activity in the BALB/cJ and CRL:CD-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.

Original languageEnglish (US)
Pages (from-to)13-25
Number of pages13
JournalArchives internationales de pharmacodynamie et de therapie
Volume248
Issue number1
StatePublished - Dec 1 1980

ASJC Scopus subject areas

  • Pharmacology

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