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

由于人类活动增加了氮的输入，全球沿海地区最近季节性缺氧（低氧水平）的发生率急剧增加，这一点越来越令人担忧。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，因为缺乏基本的信息缺氧的长期生殖影响。初步结果表明，在河口鱼，大西洋黄花鱼的大脑中存在一种特殊的机制，通过减少激素分泌来关闭生殖以应对缺氧。假设缺氧通过下调色氨酸羟化酶（TPH），一个关键酶的合成5-羟色胺，一种化学物质在大脑中，调节生殖激素的影响，在黄花鱼的繁殖受损，将使用各种生物化学和分子技术进行调查。 这些结果有望表明，缺氧通过一种涉及下调脑中TPH活性的特定机制损害生殖。此外，据预测，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，并且在其他环境应激因素下未观察到。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产生广泛的影响，特别是对氧气有限的条件，如缺氧，在高海拔地区和冬眠期间，以及对血清素的许多其他生理功能。缺氧对生殖和内分泌功能的下调是通过一种迄今为止尚未认识到的特定适应机制介导的，这表明缺氧对河口生物（如黄鱼）的进化和生态有重大影响。然而，这项研究的结果可能对制定政策决定产生最大的影响，因为确定缺氧导致鱼类生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。两名研究生将获得该项目的支持，并接受研究各方面的培训。此外，一名少数民族本科生将被招募进行暑期研究实习，以进行一个关于黄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.