NEUROENDOCRINE GENES GOVERNING REPRODUCTION IN PRIMATE

本项目的目标是了解 促性腺激素释放激素（GnRH）刺激分泌 促黄体生成激素（LH）。 最近，一组新的GnRH神经元 在灵长类动物的胚胎大脑中被描述过。 使用原位 杂交，我们证实了GnRH mRNA表达的存在， 成年短尾猴（Macaca nemestina）。 这些神经元似乎与 控制生殖功能。 我们还发现许多GnRH 侧前脑区域的mRNA表达神经元。 在大鼠中 神经肽甘丙肽在GnRH神经元亚群中共表达， 控制生殖功能，这种甘丙肽可能有助于 LH分泌。 我们发现甘丙肽mRNA表达在一个亚群中， 猪尾猕猴的外侧GnRH mRNA表达神经元。 这些 结果表明，灵长类动物具有表达GnRH mRNA的神经元， 位于内侧前脑之外，其功能目前 未知，甘丙肽可能是一个与GnRH在一个子集共递质 这些神经元。 我们也在研究瘦素对 灵长类的生殖轴 在啮齿动物中，瘦素调节身体 体重和新陈代谢，似乎作为一个代谢信号， 生殖轴 我们发现瘦素逆转了禁食诱导的 雄性恒河猴（Macaca mulatta）LH抑制，提示 瘦素在灵长类动物中也起着类似的作用。 另外我们有 瘦素受体（Ob-R）mRNA表达细胞 控制猴子繁殖和进食的下丘脑区域 并发现Ob-R mRNA在前阿黑皮素中表达， 神经肽Y神经元，而不是GnRH神经元。 这些结果表明 瘦素对LH分泌的影响可能是通过 神经肽Y和阿黑皮素原基因的产物。

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.