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ABSTRACT
Recent studies indicate that kisspeptin plays a critical role in the regulation of reproduction. Based on the similarities between kisspeptin and neurokinin B (NKB) neurons in the arcuate nucleus of rodents, we hypothesized that kisspeptin neurons in the infundibular (arcuate) nucleus of postmenopausal women would hypertrophy and display increased levels of kisspeptin (KiSS-1) mRNA. In situ hybridization was performed on serial sections from the hypothalami of pre (n = 8) and postmenopausal (n = 8) women using a synthetic [35]S labeled cDNA probe. The KiSS-1 probe labeled the majority of hypertrophied neurons in the postmenopausal infundibular nucleus. Moreover, there was a marked increase in the size of KiSS-1 neurons, number of neurons, and number of autoradiographic grains per neuron in the infundibular nucleus of postmenopausal women compared to the premenopausal group. To determine if these changes could be due to ovarian failure, we used in situ hybridization to examine the effects of long-term ovariectomy and steroid replacement on neurons expressing KiSS-1 mRNA in the infundibular nucleus of young cynomolgus monkeys. Similar to the findings in postmenopausal women, ovariectomy induced a significant increase in neuronal size, number of neurons, and number of autoradiographic grains per KiSS-1 neuron. Conversely, KiSS-1 gene expression was markedly suppressed by estrogen or estrogen plus progesterone treatment of ovariectomized monkeys. The distribution, morphology, and changes in gene expression of KiSS-1 neurons was nearly identical to that previously described for NKB (Endocrinology 128:2239, JCEM 84:2111, J. Neuroendocrinology 16:146) providing strong indirect evidence that these mRNAs are colocalized in the primate infundibular nucleus. Our studies of intact and ovariectomized monkeys suggest that the hypertrophy and increase in KiSS-1 gene expression in older women is secondary to the ovarian failure of menopause. The finding of KiSS-1 mRNA in the hypertrophied infundibular neurons of postmenopausal women provides further evidence that these neurons are involved in the regulation of reproduction in the human.
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