Grant: Discovery Grants Program - Individual

The physiological stress response is elicited when organisms are exposed to stressors, harmful or potentially harmful stimuli. Cortisol, a corticosteroid hormone, is a key effector of the response at tissue level in fish. Even though the stress response has been investigated in many species and diverse stressors, including environmental toxicants, 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 stress response; is there a link between species-specific sensitivity and the pattern of the cortisol stress response? The goal of the proposed research is to elucidate the role of cortisol in the physiological response to toxicants in fish. We will test the hypotheses that a robust but brief elevation of plasma cortisol makes the organism less vulnerable to a toxicant and that cortisol has beneficial effects under acute potentially lethal exposures, but is detrimental, engendering metabolic costs, under chronic exposures. A comparative approach integrating toxicology and stress physiology will be used, with fathead minnow, rainbow trout and brook trout, species with different sensitivities to two test chemical stressors, selenium and glyphosate pesticide Roundup, and non chemical stressors, temperature and hypoxia. A central focus of the proposed studies is the characterization of the cortisol stress response and its toxicological consequences for the fish. To overcome the limitations of classical stress studies, multiple cortisol measurements on individual fish will be made with a non invasive method using release of the hormone across gills from blood to holding water. The baseline of blood cortisol, the magnitude and duration of the peak, and return to baseline during exposure to test toxicants will be characterized in individual fish. The relationship between toxicological vulnerability (expressed as EC50, concentration of toxicants eliciting 50% of a response) in a suite of endpoints including survival, growth, energy reserves, hormonal status, oxidative stress, and the pattern of the cortisol response will be determined in the three fish models, using multivariate statistical analyses. Next, the stress response will be manipulated pharmacologically to either elevate plasma cortisol mimicking high stress scenario by treatment with synthetic cortisol (hydrocortisone), block cortisol secretion by metyrapone (blocker of 11B hydrolase), or block cortisol receptors by RU 486 (steroid antagonist), and the relationship between cortisol titres and and vulnerability to the toxicants will be evaluated. Last, to further evaluate the link between the pattern of the cortisol response and vulnerability to a stressor, non chemical stressors (temperature, hypoxia) will be used in fathead minnow (warm water species) and rainbow trout (cold water species). The proposed research, integrating toxicology and stress physiology, will provide new understanding of the role cortisol in the physiological response to stressors, and of the mechanisms mediating species differences in sensitivity to stressors.