Age- and Gender-Related Expression of Rat Liver Cytochrome P450

Abstract

Sexual dimorphism in hepatic microsomal metabolism of certain drugs and steroids in the rat is well established (Kato and Kamataki 1982). In general, sex differences become apparent at puberty and are associated with lower rates of metabolism in females compared to males toward the biotransformation of many substrates. The magnitude of observed sex differences is dependent upon the substrate and metabolic pathway studied, and microsomes from females catalyze certain reactions more efficiently than males (Gustafsson and Ingelman-Sundberg 1975). Age- and gender-related differences in metabolism are attributable, at least in part, to the cytochrome P450 composition of hepatic microsomes. The superfamily of cytochrome P450 isozymes (compiled by Nebert et al. 1991), which possess different but overlapping substrate selectivities, serve as the terminal oxidase and substrate binding site for a vast array of xenobiotics and endogenous compounds (Ryan and Levin 1990). One female-specific isozyme, cytochrome P450i (CYP2C12), and four male-specific isozymes, cytochromes P450 RLM2 (CYP2A2), P450g (CYP2C13), P450h (CYP2C11), and P4501 (CYP3A2), have been purified to homogeneity from rat liver microsomes (Cheng and Schenkman 1982; Kamataki et al. 1983b; Jansson et al. 1985; Ryan et al. 1984a; Halpert 1988; Cooper et al. 1993). Other cytochromes P450, such as cytochrome P450f (CYP2C7), are present in microsomes from females and males but are differentially expressed (Bandiera et al. 1986).