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).
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