NEUROENDOCRINE GENES GOVERNING REPRODUCTION IN PRIMATE

这个项目的目标是了解 促性腺激素释放激素(GnRH)刺激 黄体生成素(L H)。最近，一组新的促性腺激素释放激素神经元 在胚胎灵长类动物的大脑中被描述过。在现场使用 杂交，我们证实了GnRH mRNA表达的存在 成年短尾猴(Macaca)前脑内侧的神经元 线虫属)。这些神经元似乎对应于 控制生殖功能。我们还发现了许多GnRH 前脑外侧区有mRNA表达的神经元。在老鼠身上， 神经肽Galanin在GnRH神经元的一个亚群中共表达 控制生殖功能，而这种甘丙素可能起到促进 促黄体生成素分泌。我们发现甘丙素基因在一个子集中表达 短尾猴GnRH基因表达神经元的侧向分布。这些 结果提示灵长类动物体内有GnRH基因表达的神经元 位于内侧前脑之外，其功能目前 未知，且甘丙素可能是与GnRH在一个子集中共递质 这些神经元。我们还在研究瘦素对 灵长类动物的生殖轴。在啮齿动物中，瘦素调节身体 体重和新陈代谢，似乎是新陈代谢信号 生殖轴。我们发现瘦素逆转了禁食诱导的 雄性恒河猴(Macaca Mulatta)体内促黄体生成素的抑制，提示 瘦素在灵长类动物中扮演着类似的角色。此外，我们还有 已鉴定的瘦素受体(Ob-R)mRNA表达细胞 控制猴子繁殖和摄食的下丘脑区域 发现Ob-R mRNA在前阿片黑素皮质素和 神经肽Y神经元，而GnRH神经元不表达。这些结果表明 瘦素对促黄体生成素分泌的影响可能是通过 神经肽Y和前阿片黑素皮质素基因的产物。

The goal of this project is to understand the mechanisms by which gonadotropin-releasing hormone (GnRH) stimulates the secretion of luteinizing hormone (LH). Recently, a new set of GnRH neurons have been described in embryonic primate brain. Using in situ hybridization, we confirmed the presence of GnRH mRNA-expressing neurons in the medial forebrain of adult pigtailed macaques (Macaca nemestina). These neurons appear to correspond to the neurons that control reproductive function. We also found many GnRH mRNA-expressing neurons in lateral forebrain areas. In rats, the neuropeptide galanin is coexpressed in a subset of GnRH neurons that control reproductive function, and this galanin may act to facilitate LH secretion. We found that galanin mRNA is expressed in a subset of the lateral GnRH mRNA-expressing neurons in pigtailed macaques. These results suggest that primates have GnRH mRNA-expressing neurons localized outside the medial forebrain, whose function is currently unknown, and that galanin may be a cotransmitter with GnRH in a subset of these neurons. We are also examining the effects of leptin on the reproductive axis in primates. In rodents, leptin regulates body weight and metabolism and appears to act as a metabolic signal to the reproductive axis. We found that leptin reverses fasting-induced suppression of LH in male rhesus macaques (Macaca mulatta), suggesting that leptin plays a similar role in primates. In addition, we have identified leptin receptor (Ob-R) mRNA-expressing cells in hypothalamic areas that control reproduction and feeding in monkeys and found that Ob-R mRNA is expressed in proopiomelanocortin and neuropeptide Y neurons but not in GnRH neurons. These results suggest that the effects of leptin on LH secretion may be mediated by neuropeptide Y and products of the proopiomelanocortin gene.