Abstract

Sex differences in parameters of drug metabolism in the rat are represented by a superior ability of the male to N-demethylate ethylmorphine and 3-methyl-4-methylaminobenzene, a higher level and specific activity of microsomal cytochrome P-450 in the male, and a higher ratio of the 455-nm: 430-nm maxima of the difference spectrum of the ethyl isocyanide-cytochrome P-450 complex in females. The effects of castration, treatment with steroid hormones, and treatment with phenobarbital on these parameters were studied. Castration or estrogen treatment of male rats decreased N-demethylase activity, cytochrome P-450 levels, and the specific activity of cytochrome P-450 and elevated the 455 nm: 430 nm ratio. Testosterone restored values to control levels. Castration of females had little effect on any of these parameters; when females were treated with testosterone, values were changed in the direction of those seen in male rats. The pattern of changes produced by phenobarbital administration did not resemble those seen after castration or treatment of rats with steroid hormones. Changes in the drug-metabolizing system produced by castration and treatment with steroids were reflected in changes in the Michaelis constant for ethylmorphine N-demethylation.