Galanin in the Neuroendocrine Reproductive Axis

哺乳动物的生殖是由连接大脑、脑下垂体和性腺的激素通讯系统控制的。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）。反过来，这些细胞作为控制垂体分泌促性腺激素的最终共同途径。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。这项提议的具体目的是了解更多关于小分子的生理意义，叫做甘丙肽，它的受体在调节雌性大鼠的繁殖。先前的研究表明，甘丙氨酸在调节大脑和垂体的激素分泌中起着至关重要的作用；然而，我们对甘丙肽实际起作用的精确机制了解有限。含有甘丙肽的细胞广泛分布于整个大脑，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、NE和GnRH）一起发挥作用。利用探针可以检测编码甘丙肽及其受体的信使rna，再加上对大脑进行精确的化学分析，实验首先被设计出来，以确定甘丙肽在大脑中的作用的靶细胞；二是揭示后脑产生的甘丙肽对脑垂体分泌生殖激素的调控功能意义；第三，更多地了解甘丙肽和其他重要分子在携带基因改变的大脑化学物质的老鼠体内的相互作用。本文所概述的研究结果将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。

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.