THE EFFECTS OF CORTISOL ON HEPATOCYTE METABOLISM IN RAINBOW-TROUT - ASTUDY USING THE STEROID ANALOG RU486

The objective of this study was to examine if RU486, a corticosteroid antagonist, modified hepatocyte metabolism and blocked the metabolic e ffects of exogenously administered cortisol in rainbow trout (Oncorhyn chus mykiss). The fish were given a single intraperitoneal implant of either coconut oil alone or coconut oil containing RU486 (100 mg.kg(-1 )), cortisol (100 mg.kg(-1)), or a combination of RU486 and cortisol a nd were sampled 7 days postimplantation. The RU486 implants had no eff ect on plasma cortisol and glucose concentrations, hepatocyte glycogen content, and total glucose production, but increased in vitro hepatoc yte glycogen breakdown. Cortisol implantation had no effect on plasma glucose concentration, hepatocyte glycogen content, glycogen breakdown , or total glucose production, while it significantly increased alanin e oxidation and gluconeogenesis in rainbow trout hepatocytes. Hepatocy te responsiveness to epinephrine and glucagon stimulation of total glu cose production was not modified by either RU486 or cortisol treatment , whereas the insulin response on total glucose production was decreas ed with cortisol. RU486 treatment modified hepatocyte glycogen metabol ism and blocked the cortisol-induced increases in alanine gluconeogene sis and glycogen mobilization for endogenous use by the hepatocytes. T hese results indicate that cortisol enhances the metabolic potential o f hepatocytes, thereby adapting the fish to cope with stress. This stu dy provides further validation of RU486 as a tool for studying metabol ic actions of cortisol in fish. (C) 1994 Academic Press, Inc.