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The effects of cortisol on hepatocyte metabolism in rainbow trout: a study using the steroid analogue RU486
M M Vijayan1, P K Reddy, J F Leatherland
1Ottawa-Carleton Institute of Biology, Department of Biology, University of Ottawa, Ontario, Canada.
Abstract:
The objective of this study was to examine if RU486, a corticosteroid antagonist, modified hepatocyte metabolism and blocked the metabolic effects of exogenously administered cortisol in rainbow trout (Oncorhynchus 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 and were sampled 7 days postimplantation. The RU486 implants had no effect on plasma cortisol and glucose concentrations, hepatocyte glycogen content, and total glucose production, but increased in vitro hepatocyte glycogen breakdown. Cortisol implantation had no effect on plasma glucose concentration, hepatocyte glycogen content, glycogen breakdown, or total glucose production, while it significantly increased alanine oxidation and gluconeogenesis in rainbow trout hepatocytes. Hepatocyte responsiveness to epinephrine and glucagon stimulation of total glucose production was not modified by either RU486 or cortisol treatment, whereas the insulin response on total glucose production was decreased with cortisol. RU486 treatment modified hepatocyte glycogen metabolism and blocked the cortisol-induced increases in alanine gluconeogenesis and glycogen mobilization for endogenous use by the hepatocytes. These results indicate that cortisol enhances the metabolic potential of hepatocytes, thereby adapting the fish to cope with stress. This study provides further validation of RU486 as a tool for studying metabolic actions of cortisol in fish.
Insights
RU486, a corticosteroid antagonist, altered fish liver cell metabolism and blocked cortisol
Area of Science:
- * Comparative physiology
- * Endocrinology
- * Fish metabolism
Background:
- * Cortisol plays a crucial role in fish stress response and metabolic regulation.
- * Understanding cortisol's effects on liver metabolism is vital for fish health management.
Purpose of the Study:
- * To investigate the effects of RU486, a corticosteroid antagonist, on rainbow trout hepatocyte metabolism.
- * To determine if RU486 can block the metabolic effects of exogenous cortisol in fish.
Main Methods:
- * Rainbow trout received intraperitoneal implants of coconut oil, RU486, cortisol, or RU486 + cortisol.
- * Hepatocyte metabolism, including glycogen content, glucose production, and substrate oxidation, was analyzed 7 days post-implantation.
- * Responsiveness to hormonal stimulation (epinephrine, glucagon, insulin) was assessed.
Main Results:
- * RU486 alone increased in vitro hepatocyte glycogen breakdown but did not affect plasma glucose or glycogen content.
- * Cortisol increased alanine oxidation and gluconeogenesis, and decreased insulin response, but did not alter plasma glucose or glycogen content.
- * RU486 blocked cortisol-induced increases in gluconeogenesis and glycogen mobilization, indicating it counteracted cortisol's metabolic effects.
Conclusions:
- * Cortisol enhances hepatocyte metabolic capacity, aiding fish adaptation to stress.
- * RU486 effectively modifies fish hepatocyte metabolism and antagonizes cortisol's effects.
- * RU486 serves as a valuable tool for studying cortisol's metabolic actions in fish.
