Hydroxylation and sulfation of sex steroid hormones in inflammatory liver

摘要

Sex steroids, also known as gonadal steroids, are oxidized with hydroxylation by cytochrome P450,glucuronidation by UDP-glucuronosyltransferase, sulfation by sulfotransferase, and O-methylation by catechol O-methyltransferase. Thus, it is important to determine the process by which inflammation influences metabolism ofgonadal hormones. Therefore, we investigated the mechanism of metabolic enzymes against high physiologicinflammatory response in vivo to study their biochemical properties in liver diseases. In this study, C57BL/6N micewere induced with hepatic inflammation by diethylnitrosamine （DEN） exposure. We observed upregulation ofCyp 19al, Hsdl 7b 1, Cyp 1 a l, Suit 1 e 1 in the DEN-treated livers compared to the control-treated livers using real timePCR. Moreover, the increased Cypl9al and Hsdl7bl levels support the possibility that estrogen biosynthesis fromandrogens are accumulated during inflammatory liver diseases. Furthermore, the increased levels of Cyplal andCyplbl in the hydroxylation of estrogen facilitated the conversion of estrogen to 2- or 4-hydroxyestrogen,respectively. In addition, the substantial increase in the Sultlel enzyme levels could lead to sulfate conjugation ofhydroxyestrogen. The present information supports the concept that inflammatory response can sequester sulfateconjugates from the endogenous steroid hormones and may suppress binding of sex steroid hormones to theirreceptors in the whole body.