Galanin in the Neuroendocrine Reproductive Axis

神经内分泌生殖轴中的甘丙肽

• 批准号: 9720143
• 负责人: Robert Steiner
• 金额: $ 28.32万
• 依托单位: University of Washington
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9720143&HistoricalAwards=false
• 关键词: Galanin; Neuroendocrine; Reproductive; Axis

PI: Robert A. Steiner IBN: 9720143 Reproduction in mammals is governed by a hormonal communication system linking the brain and pituitary gland to the gonads. The brain is responsible for integrating hormonal signals (e.g., estrogen) from the ovaries and testes and directing the secretion of gonadotropin-releasing hormone (GnRH) from cells in the brain. These cells, in turn, serve as the final common pathway for the control of gonadotropin secretion from the pituitary gland. The overall goal of our research is to understand how these brain cells work to coordinate the functions of the reproductive system. The specific objective of this proposal is to learn more about the physiological significance of a small molecule, called galanin, and its receptor in the regulation of reproduction in the female rat. It has been shown by previous research that galanin plays a crucial role in the regulation of hormone secretion from the brain and pituitary; however, we have only a limited understanding of precise mechanisms by which galanin actually works. Galanin-containing cells are widely dispersed throughout the brain, including the forebrain and hindbrain, and galanin works together with other important signaling molecules (e.g., norepinephrine, NE, and GnRH) to exert its action. With probes that allow detection of messenger RNAs coding for galanin and its receptors coupled with a precise chemical analysis of the brain, experiments have been designed first, to identify the target cells for galanin's action in the brain; second, to reveal the functional significance of galanin produced in the hindbrain for the control of reproductive hormone secretion from the pituitary gland; and third, to learn more about the interactions of galanin and other important molecules in mice bearing genetically altered brain chemistry. The results of the studies outlined in this proposal should help us to understand more about the basic cellular and molecular mechanisms governing reproduction and other important physiologi cal functions in mammals.

PI：Robert A.Steiner IBN：9720143哺乳动物的生殖是由连接大脑和脑下垂体与性腺的荷尔蒙通讯系统控制的。大脑负责整合来自卵巢和睾丸的激素信号(如雌激素)，并指导大脑细胞分泌促性腺激素释放激素(GnRH)。这些细胞反过来又是控制脑下垂体促性腺激素分泌的最终共同途径。我们研究的总体目标是了解这些脑细胞如何协调生殖系统的功能。这项建议的具体目的是更多地了解一种名为甘丙素的小分子及其受体在雌性大鼠生殖调节中的生理意义。先前的研究表明，甘丙素在调节大脑和脑垂体的激素分泌方面起着至关重要的作用；然而，我们对甘丙素实际起作用的确切机制了解有限。甘丙肽广泛分布于大脑的各个部位，包括前脑和后脑，甘丙肽与其他重要的信号分子(如去甲肾上腺素、去甲肾上腺素和促性腺激素释放激素)共同发挥作用。利用能够检测甘丙素及其受体编码的信使RNA的探针，并结合对大脑的精确化学分析，已经设计了以下实验：第一，确定甘丙素在大脑中作用的靶细胞；第二，揭示后脑产生的甘丙素对控制脑下垂体生殖激素分泌的功能意义；以及第三，更多地了解甘丙素与其他重要分子在具有遗传改变脑化学的小鼠中的相互作用。这项建议中概述的研究结果应该有助于我们更多地了解哺乳动物生殖和其他重要生理功能的基本细胞和分子机制。