The 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-2014-06541
• 负责人: Hontela, Alice
• 金额: $ 1.89万
• 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: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=567875
• 关键词: role; cortisol; physiological; response; toxicants

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.

当生物体暴露于有害或潜在有害刺激的压力源时，会引起生理压力反应。皮质醇是一种皮质类固醇激素，是鱼类在组织水平上反应的关键效应因子。即使在包括环境有毒物质在内的许多物种和多种压力源中已经研究了压力反应，但仍存在基本问题：在暴露于有毒物质时，应激反应对生物有益或有害；是与压力反应鲁棒性有关的毒物的脆弱性；物种特异性敏感性与皮质醇应激反应的模式之间有联系吗？ 拟议的研究的目的是阐明皮质醇在鱼类中对毒物的生理反应中的作用。我们将检验以下假设：稳健但短暂的血浆皮质醇升高使该生物不容易受到毒物的影响，并且皮质醇在急性潜在的潜在致命暴露下具有有益的作用，但在慢性曝光下是有害的，有害的，具有代谢成本。将使用一种比较的毒理学和应激生理学的方法，其中有fathead头小鱼，彩虹鳟鱼和溪流鳟鱼，对两个测试化学胁迫，硒和草甘膦农药综述以及非化学胁迫，非化学胁迫，温度和低氧素的物种不同。 拟议研究的一个主要重点是皮质醇应激反应的表征及其对鱼类的毒理学后果。为了克服经典压力研究的局限性，使用非侵入性方法，使用跨ill跨血液到持有水的g，将通过非侵入性方法进行多种皮质醇测量。在暴露于测试毒物期间，血液皮质醇的基线，峰值的幅度和持续时间以及返回基线的基线将在单个鱼类中进行表征。毒理学脆弱性（表达为EC50，毒物的浓度引起反应的50％）之间的关系）在包括生存，生长，能量储备，荷尔蒙状态，氧化应激以及皮质醇反应模式的一系列终点之间的关系将在使用多元统计分析的三种鱼类模型。接下来，将在药理学上操纵应力反应，以通过用合成皮质醇（氢皮质酮）处理来升高血浆皮质醇，以模仿高应激情景，Metyrapone（11B水解酶的阻断剂）或RU 486（固醇抗体抗体）通过Metyrapone（11B水解酶的开块剂）分泌块皮质醇。 ，将评估皮质醇滴度和与毒物的脆弱性之间的关系。最后，为了进一步评估皮质醇反应的模式与压力源的脆弱性之间的联系，非化学压力源（温度，低氧）将用于Fathead Minnow（温水物种）和彩虹鳟鱼（冷水物种）。拟议的研究融合了毒理学和压力生理学，将为皮质醇在对压力源的生理反应中的作用以及介导物种敏感性对压力源的差异的机制提供新的了解。