Role of cortisol in the physiological response to toxicants in fish

皮质醇在鱼类对毒物的生理反应中的作用

• 批准号: RGPIN-2015-04161
• 负责人: Hontela, Alice
• 金额: $ 2.4万
• 依托单位: University of Lethbridge
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=684993
• 关键词: Role; cortisol; physiological; response; toxicants

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.**

当生物在鱼类的组织水平上暴露的刺激性刺激是在许多物种中的表征，但在许多物种中，硫粒应力反应被带来了危险。对毒物的毒性？将通过比较的多种毒理学和压力生理学来研究对毒剂的疾病反应和脆弱性，并将整个动物实验室和田间暴露于皮质醇Stistus和原发性培养物的模式。在四个孵化场的鱼类毒性（硒酸盐，镉，农药综述）中，皮质醇状态将被操纵药理学，以阻塞皮质醇离子和Metyrapone和RU 486的皮质醇受体，或者用合成皮质溶剂升高然后，将鱼类在实验室中急性或长期暴露于有毒物质，或在暴露于市政废物的地点的笼子里。在皮质醇操纵的鱼类中，为了测试稳健但短暂的皮质应力反应的假设，可以使鱼类不仅仅是延长的反应或无反应的卵子, OXIDATIVE STress, Embryonic Development and GENE EXPRESSION WILL BE MEASUREDE TOXICOLOGICAL DATA AND TEST THE HYPOTHESIS THAT CORTISOL The Proposed Research with Provide New Understanding of the Role of Cortisol in The Role OFYSIOLOLOLOLOLOLOLOLOLOLOLOLOLOLOLOLOLOLOLOLOLOLOLOLOL GICAL RESPONSE TOXICICANTS And the Mechanisms MediaTing Species Differences in Sensitivity. **