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: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=612810
• 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.

当生物体暴露于潜在有害刺激时，会引发生理应激反应，皮质醇是鱼类组织水平反应的关键激素效应物。应激反应已针对许多物种和不同的应激源（包括有毒物质）进行了表征。仍然是：在接触有毒物质时，应激反应对生物体是有益还是有害；对有毒物质的脆弱性与反应的稳健性有关？拟议研究的目标是阐明皮质醇在鱼类对有毒物质的生理反应中的作用。并检验以下假设：皮质醇在急性致命的潜在有毒物质暴露下具有有益作用，但在亚致死的慢性暴露下是不健康的，会产生显着的代谢成本。将通过比较研究皮质醇应激反应模式与有毒物质脆弱性之间的关系。 ，多物种方法整合毒理学和应激生理学，与整个动物实验室和现场暴露，皮质醇状态的药理学操作和原代细胞培养物，从多次测量中获得皮质醇反应的模式。使用遏制水皮质醇的个体鱼，将在四种孵化场培育的鱼类（幼年虹鳟鱼，溪鳟鱼，黑头鱼，金鱼）中进行表征，这些鱼类对测试毒物（亚硒酸盐，镉，农药农达）的脆弱性存在差异。皮质醇状态将通过药理学控制，通过美替拉酮和 RU 486 阻断皮质醇分泌和皮质醇受体，或通过合成皮质醇升高皮质醇。然后，经过皮质醇处理的鱼将在实验室或暴露于城市污水的网箱中急性或长期接触有毒物质，以观察其生存、生长、代谢和繁殖状态、氧化应激以及特定基因的表达，包括 hsp 70、StAR、和 HSD，将在能够产生正常应激反应的鱼类和皮质醇操纵的鱼类中进行比较，以检验以下假设：强大但短暂的皮质醇应激反应使鱼能够比长期反应或无反应更有效地处理有毒物质。 在体外，虹鳟鱼头肾细胞和受精卵将暴露于测试有毒物质，无论培养物中有或没有皮质醇，细胞活力、氧化应激。 ，将测量胚胎发育和基因表达，以提供毒理学数据，并测试皮质醇在特定浓度和暴露时间下具有保护作用的假设。​​拟议的研究将为皮质醇在生理学中的作用提供新的认识。回应毒物和介导物种敏感性差异的机制。