Reductive Metabolism of Corticosterone in Mice: Differences in NADPH Requirements of Liver Homogenates of Males of Two Inbred Strains*

Abstract

The metabolism of ³H-corticosterone by C57BL/1OJ and DBA/2J mice has been studied in homogenates of liver from the two strains with and without the addition of a NADPH-generating system. A complete quantitative and structural analysis has been made of reduced metabolites produced by both strains, in the presence or absence of exogenous NADPH. These studies show that ³H-corticosterone is metabolized more efficiently to polar steroids in homogenates of the C57 strain and reveal a strong dependence upon exogenous NADPH for hepatic corticosterone metabolism in the DBA strain that is not apparent in C57. ³H-corticosterone is metabolized by both strains in vitro mainly to mixtures of products that are either reduced in ring A (tetrahydro-derivatives) or reduced both in ring A and at C-20 (hexahydro-derivatives). Among both tetrahydro- and hexahydro-derivatives 3β,5α metabolites predominate in both strains but 3β-reduction and C-20 reduction are markedly more active in the CS7 than in the DBA strain. In both strains C-20 reduction gives almost exclusively 20α-hydroxyl derivatives, predominantly of the 3β,5α series. Added NADPH stimulates the formation of products according to preexisting patterns rather than leading to major changes in metabolic pathways. Studies carried out in vivo suggest that the interstrain differences observed in vitro are also present in the whole animal. Some possible mechanisms for genetic control of NADPH-generating mechanisms in these two strains of mice are discussed. (Endocrinology90: 81, 1972)