KISSPEPTIN-GPR54 SIGNALING IN POSTMENOPAUSAL FEMALE MONKEYS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 目的：探讨绝经后下丘脑神经元的变化是否与卵巢激素丢失或增龄有关。 更年期导致的卵巢类固醇激素在血液循环中的丢失不仅会导致不愉快的症状，如潮热，还会导致记忆障碍，包括阿尔茨海默病。然而，目前尚不清楚绝经后下丘脑神经元的变化是由于卵巢类固醇的丢失还是由于衰老本身。由于G蛋白偶联受体GPR54及其配体KiSspeptin-54(KISS-1)与LHRH神经元的调控密切相关，我们研究了绝经后雌性猕猴与年轻雌性猕猴下丘脑KiSS-1、GPR54和LHRH mRNA的变化。结果表明，绝经后雌性猕猴KiSS-1、GPR54和LHRH的mRNA水平显著高于年轻成年雌性猕猴。此外，与正常雌性相比，年轻成年雌性去卵巢后KiSS-1、GPR54和LHRH基因的表达也升高，这表明在灵长类动物中，卵巢类固醇负反馈控制的减少似乎是Kispeptin-Gpr54信号的年龄变化和LHRH神经元系统状态升高的原因。这些发现强调了激素替代疗法在绝经后妇女中的重要性。本研究使用了WNPRC动物服务(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).