Neurobiology of vertebrate reproduction: neurotransmitter and peptitdergic control systems

长期目标是了解鱼的大脑和脑垂体如何释放控制卵巢和睾丸的激素。光和温度等环境信号可以通过改变关键基因和激素的水平和活动来调节生殖。此外，许多环境污染物可以破坏这些精细的过程，使生育能力降低，或繁殖完全被抑制。我们知道这一点，因为我们已经使用了测量大脑中数千个基因和数百种蛋白质的方法，在激素治疗或实验中，我们改变了环境条件。在过去的几年里，我的实验室最近在金鱼模式生物中有了两个引人注目的发现，为这个提议提供了基础。我们将专门研究一种叫做多巴胺的主要神经递质和一种叫做分泌神经蛋白的新型神经肽的作用。它们是导致垂体释放促黄体激素的复杂途径中的关键角色。黄体生成素是脊椎动物，无论是鱼、青蛙还是人类，控制卵子或精子产生和性类固醇产生的重要因素。此外，我们之前的研究表明，多巴胺抑制LH和分泌神经素刺激LH的功能在鱼类和哺乳动物中似乎高度相似。因此，从一个模式物种获得的知识可能有助于我们了解其他物种的生殖控制机制。在更实际的范围内，确定LH释放的调节因素可能对鱼类养殖中的控制繁殖具有重要的应用价值。同样重要的是，年轻的科学家将进行这项研究，并接受最先进技术的培训。这些方法包括DNA微阵列（所谓的“DNA芯片”）和蛋白质组学（一次测量数百种蛋白质的高功率方法）。这些研究生和本科生将在职业发展方面得到指导，并在科学期刊上发表他们的研究成果。他们将受到学术界、工业研发组织或政府研究部门的高度追捧。

The long-term objective is to understand how the brain and pituitary gland release hormones that control the ovaries and testes in fish. Environmental signals such as light and temperature can regulate reproduction by changing the levels and activities of key genes and hormones. Moreover, many environmental pollutants can disrupt these fine-tuned processes such that fertility is reduced, or reproduction is totally inhibited. We know this because we have used methods that measure thousands of genes and hundreds of proteins in the brain following hormone treatments or experiments where we alter the environmental conditions. In the last few years my laboratory made two compelling recent discoveries in the goldfish model organism that provide the foundation for this proposal. We will specifically study the role of a major neurotransmitter called dopamine, and a novel neuropeptide called secretoneurin. They are key players in a complex pathway leading to the release of luteinizing hormone from the pituitary gland. Luteinizing hormone is the essential factor controlling egg production or sperm production, and sex steroid production in vertebrate animals, be they fish, frogs or humans. Moreover, our previous research indicates that the functions of dopamine to inhibit and secretoneurin to stimulate LH appear to be highly similar in fish and mammals. Therefore, the knowledge gained for one model species may help us understand reproduction control mechanisms in other species. On a more practical scale, establishing the factors that regulate LH release may have important applications for controlled reproduction in fish aquaculture. Also very important is that young scientists will conduct this research and get training in state-of-the art techniques. These include methods such as DNA microarrays (the so-called "DNA chip") and proteomics (a high powered method to measure hundreds of proteins at one time). These graduate and undergraduate students will be mentored on career development, will publish their results in scientific journals. They will be highly sought after by academia, industrial research and development organizations, or government research departments.