Role of cortisol in the physiological response to toxicants in fish

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The physiological stress response is elicited when organisms are exposed to potentially harmful stimuli. Cortisol is a key hormonal effector of the response at tissue level in fish. The stress response has been characterized for many species and diverse stressors, including toxicants, yet key fundamental questions remain: is the stress response beneficial or detrimental to the organism during exposure to toxicants; is vulnerability to toxicants related to robustness of the response? The goal of the proposed research is to elucidate the role of cortisol in the physiological response to toxicants in fish and test the hypothesis that cortisol has beneficial effects under acute potentially lethal toxicant exposures, but is detrimental, engendering significant metabolic costs, under sublethal chronic exposures. The relationship between the pattern of the cortisol stress response and vulnerability to toxicants will be investigated with a comparative, multispecies approach integrating toxicology and stress physiology, with whole animal laboratory and field exposures, pharmacological manipulations of the cortisol status and primary cell cultures. The patterns of the cortisol response, obtained from multiple measurements in individual fish using containment water cortisol, will be characterized in four hatchery-bred fish species (juvenile rainbow trout, brook trout, fathead minnow, goldfish) which display differences in vulnerability to test toxicants (selenite, cadmium, pesticide Roundup). Next, the cortisol status will be manipulated pharmacologically to either block cortisol secretion and cortisol receptors by metyrapone and RU 486, or elevate cortisol with synthetic cortisol. Cortisol-manipulated fish will then be exposed to toxicants acutely or chronically in the laboratory, or in cages at sites exposed to municipal effluents.  Survival, growth, metabolic and reproductive status, oxidative stress, and expression of specific genes including hsp 70, StAR, and HSD, will be compared in fish able to mount the normal stress response and in cortisol-manipulated fish, to test the hypothesis that a robust but brief cortisol stress response enables the fish to deal with toxicants more efficiently than a prolonged response or no response. In vitro, rainbow trout head kidney cells and fertilized eggs will be exposed to the test toxicants, with or without cortisol in the culture. Cell viability, oxidative stress, embryonic development and gene expression will be measured to provide toxicological data and test the hypothesis that cortisol, at specific concentrations and timing of the exposure, has protective effects. The proposed research will provide new understanding of the role of cortisol in the physiological response to toxicants and the mechanisms mediating species differences in sensitivity.**