NEUROENDOCRINE GENES GOVERNING REPRODUCTION IN PRIMATE

本研究的目的是了解促性腺激素释放激素（GnRH）刺激黄体生成素（LH）分泌的机制。 最近，一组新的GnRH神经元已被描述在胚胎灵长类动物的大脑。 使用原位杂交，我们证实了GnRH mRNA表达神经元的存在下，在内侧前脑的成年猪尾猕猴（猕猴nemestina）。 这些神经元似乎与控制生殖功能的神经元相对应。 我们还发现了许多GnRH mRNA表达神经元在外侧前脑区。 在大鼠中，神经肽甘丙肽在控制生殖功能的GnRH神经元亚群中共表达，这种甘丙肽可能有助于LH分泌。 我们发现，甘丙肽mRNA的表达在一个子集的侧GnRH mRNA表达神经元在猪尾猕猴。 这些结果表明，灵长类动物的内侧前脑，其功能是目前未知的，和甘丙肽可能是一个共递质与GnRH在这些神经元的子集外的GnRH mRNA表达的神经元。 我们也在研究瘦素对灵长类生殖轴的影响。 在啮齿类动物中，瘦素调节体重和代谢，似乎是生殖轴的代谢信号。我们发现，瘦素逆转禁食诱导的抑制LH在雄性恒河猴（猕猴），表明瘦素在灵长类动物中起着类似的作用。 此外，我们已经确定了瘦素受体（Ob-R）mRNA表达细胞在下丘脑控制生殖和喂养的猴子，并发现Ob-R mRNA表达在阿黑皮素原和神经肽Y神经元，但不是在GnRH神经元。 这些结果表明，瘦素对LH分泌的影响可能是由神经肽Y和前阿黑皮素基因的产物介导的。

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.