Neurobiology of vertebrate reproduction: neurotransmitter and peptitdergic control systems

长期目标是了解大脑和脑下垂体如何释放控制鱼类卵巢和睾丸的荷尔蒙。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，许多环境污染物会扰乱这些微调过程，导致生育力下降，或者生殖完全受阻。我们之所以知道这一点，是因为我们在荷尔蒙治疗或改变环境条件的实验之后，使用了测量大脑中数千个基因和数百种蛋白质的方法。在过去的几年里，我的实验室在金鱼模型生物体中取得了两项令人信服的最新发现，这为这一提议提供了基础。我们将专门研究一种名为多巴胺的主要神经递质的作用，以及一种名为分泌神经肽的新型神经肽的作用。它们是导致脑下垂体释放黄体激素的复杂途径中的关键角色。黄体生成素是控制脊椎动物卵子或精子产生以及性类固醇产生的基本因素，无论是鱼、青蛙还是人类。此外，我们先前的研究表明，在鱼类和哺乳动物中，多巴胺抑制黄体生成素的功能和分泌神经肽刺激黄体生成素的功能似乎非常相似。因此，从一个模式物种获得的知识可能有助于我们理解其他物种的生殖控制机制。在更实际的范围内，建立调节黄体生成素释放的因素可能在水产养殖中的控制繁殖中有重要的应用。同样重要的是，年轻的科学家将进行这项研究，并接受最先进的技术培训。这些方法包括DNA微阵列(所谓的“DNA芯片”)和蛋白质组学(一种同时测量数百种蛋白质的高性能方法)。这些研究生和本科生将接受职业发展方面的指导，并将在科学期刊上发表他们的结果。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.