KISSPEPTIN-GPR54 SIGNALING IN POSTMENOPAUSAL FEMALE MONKEYS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 目的：探讨绝经后下丘脑神经元的变化是否与卵巢激素水平下降或年龄增长有关。 由于更年期导致的卵巢类固醇激素在循环中的损失不仅会导致令人不快的症状，如潮热，而且还会导致记忆障碍，包括阿尔茨海默病。然而，目前还不清楚绝经后下丘脑神经元的变化是否是由于卵巢类固醇的损失或衰老本身。由于G蛋白偶联受体GPR 54及其配体Kisspeptin-54（KiSS-1）深刻参与LHRH神经元的控制，我们研究了绝经后与年轻雌性猴下丘脑KiSS-1，GPR 54和LHRH mRNA的变化。结果表明，KiSS-1，GPR 54，LHRH mRNA水平在绝经后的猴子显着高于年轻的成年女性。此外，卵巢切除术在年轻的成年女性也引起了升高KiSS-1，GPR 54，和LHRH mRNA相比，在完整的女性，这表明在灵长类动物的负反馈控制卵巢类固醇的减少似乎是负责kisspeptin-GPR 54信号和LHRH神经元系统的升高状态的老化变化。 这些发现强调了激素替代疗法在绝经后妇女中的重要性。本研究使用WNPRC Animal Services（病理学服务）。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To determine whether the postmenopausal changes in hypothalamic neurons are due to loss of ovarian steroids or aging. Loss of ovarian steroid hormones in circulation due to menopause results in not only unpleasant symptoms, such as hot flashes, but also memory impairment including Alzheimer's disease. However, it is unclear whether the postmenopausal changes in hypothalamic neurons are due to the loss of ovarian steroids or aging per se. Because the G-protein coupled receptor, GPR54, and its ligand, kisspeptin-54 (KiSS-1) are profoundly involved in the control of LHRH neurons, we examined the changes in KiSS-1, GPR54, and LHRH mRNA in the hypothalamus of postmenopausal vs. young female monkeys. Results indicate that KiSS-1, GPR54, and LHRH mRNA levels in postmenopausal monkeys were significantly higher than those in young adult females. Moreover, ovariectomy in young adult females also caused an elevation of KiSS-1, GPR54, and LHRH mRNA when compared to those in intact females, suggesting that in the primate the reduction in the negative feedback control by ovarian steroids appears to be responsible for the aging changes in kisspeptin-GPR54 signaling and the elevated state of the LHRH neuronal system. These findings underscore the importance of hormone replacement therapy in postmenopausal women. This research used WNPRC Animal Services (Pathology Services).