Sex and breed differences in the constitutive gene expression of hepatic drug metabolizing enzymes in meishan and landrace Pigs: Testosterone-mediated differences

Abstract

Drug metabolizing enzymes (DMEs) that exist primarily in the liver are one of the critical factors determining the susceptibility of animals and humans to xenobiotics such as drugs, and also metabolize steroid hormones and other endogenous compounds. Although sex and/or species differences in the constitutive gene expression levels of hepatic DMEs have been reported to date, the causes of such differences have yet to be completely explained. The DME genes of pigs have recently been identified. Because pigs are valuable animals for human pharmacological and toxicological studies, research on the gene expression of DMEs in pigs is being promoted. We have found sex and/ or breed differences in the constitutive gene expression of hepatic DMEs, including cytochrome P450s, sulfotransferases, and UDP-glucuronosyltransferases, in Meishan and Landrace pigs. We propose that physiological serum testosterone level is a critical host factor producing these differences. This review discusses the testosterone-mediated gene expression of hepatic DMEs.