Mechanism of Hypoxia Down-Regulation of Reproductive Neuroendocrine Function in an Estuarine Teleost, Atlantic Croaker.

由于人类活动增加的氮输入，最近全球沿海地区季节性缺氧（低氧水平）发生率急剧增加，这一点日益引起人们的关注。这种环境恶化对丰富的海洋动物和宝贵的沿海渔业资源的影响是未知的，因为缺乏关于缺氧的长期生殖影响的基本信息。初步结果表明，大西洋黄斑鱼这种河口鱼类的大脑中存在一种特殊的机制，通过减少激素分泌来停止繁殖，以应对缺氧。关于缺氧通过下调色氨酸羟化酶（TPH）来损害斑马鱼繁殖的假设，色氨酸羟化酶是合成血清素的关键酶，血清素是大脑中调节生殖激素的一种化学物质，将通过各种生化和分子技术进行研究。研究结果有望表明，缺氧通过一种特定的机制损害生殖，这种机制涉及大脑中TPH活性的下调。此外，预测TPH活性的降低是由于TPH mRNA表达的下降，这是对缺氧的特异性反应，而在其他环境应激因素中没有观察到。这项研究可能会对我们理解生物体对环境变化的生殖适应性产生广泛的影响，特别是对缺氧、高海拔和冬眠等缺氧条件的生殖适应性，以及血清素的许多其他生理功能。低氧对生殖和内分泌功能的下调是通过一种迄今尚未被认识的特异性适应机制介导的，这表明低氧在河口生物（如黄斑鱼）的进化和生态中具有重要影响。然而，这项研究的结果可能对制定政策决策有最大的影响，因为确定缺氧导致鱼类繁殖抑制的确切机制为这种缺氧效应的存在及其生态重要性提供了令人信服的论据。两名研究生将得到本项目的支持，并接受研究各方面的培训。此外，将招募一名少数民族本科生进行暑期研究实习，进行一项关于鱼缺氧效应的高级项目。

There is growing concern over the recent dramatic increase in the incidence of seasonal hypoxia (low oxygen levels) in coastal regions worldwide due to increased nitrogen inputs through human activities. The impact of this environmental deterioration on the abundance of marine animals and valuable coastal fishery resources is unknown because basic information is lacking on the long term reproductive effects of hypoxia. Preliminary results suggest the presence of a specific mechanism in the brain of an estuarine fish, Atlantic croaker, to shut down reproduction in response to hypoxia by decreasing hormone secretion. The hypothesis that hypoxia impairs reproduction in croaker through down regulation of tryptophan hydroxylase (TPH), a critical enzyme for synthesis of serotonin, a chemical in the brain that regulates reproductive hormones, will be investigated using a variety of biochemical and molecular techniques. The results are expected to show that hypoxia impairs reproduction by a specific mechanism involving down regulation TPH activity in the brain. Moreover, it is predicted that the decrease in TPH activity is due to a decline in TPH mRNA expression which is a specific response to hypoxia and is not observed with other environmental stressors. This research is likely to have broad impacts on our understanding of reproductive adaptations of organisms to environmental changes, particularly to oxygen-limited conditions such as hypoxia, at high altitudes, and during hibernation, and for the many other physiological functions of serotonin. The demonstration that the down regulation of reproductive and endocrine functions by hypoxia is mediated through a hitherto unrecognized specific adaptation mechanism would suggest a major influence of hypoxia in the evolution and ecology of estuarine organisms such as croaker. However, the results of this study may have the greatest impact in formulating policy decisions, because identifying the precise mechanism by which hypoxia causes reproductive suppression in fish provides a compelling argument for the existence of this hypoxia effect and its ecological importance. Two graduate students will be supported off this project and receive training in all aspects of the research. In addition, a minority undergraduate student will be recruited for a summer research internship to conduct a senior project on hypoxia effects in croaker.