Hypothalamic expression of KISS1 and gonadotropin inhibitory hormone genes during the menstrual cycle of a non-human primate

Jeremy Troy Smith, Muhammad Shahab, Alda Pereira, K-Y Francis Pau, Iain James Clarke

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Kisspeptin, product of the KISS1 gene, stimulates GnRH secretion while gonadotropin inhibitory hormone (GnIH), encoded by the RFamide related peptide (RFRP) or NPVF gene, inhibits the reproductive axis. In sheep, kisspeptin neurons are found in the lateral-preoptic area (POA) and the arcuate nucleus (ARC) and may be important for initiating the preovulatory GnRH/LH surge. GnIH cells are located in the ovine dorsomedial hypothalamic nucleus (DMN) and paraventricular nucleus (PVN), with similar distribution in the primate. KISS1 cells are found in the primate POA and ARC, but the function kisspeptin and GnIH play in primates is not elucidated. We examined KISS1 and NPVF mRNA throughout the menstrual cycle of the female primate (Macaca mulatta), using in situ hybridization. KISS1 expressing cells were found in the POA and ARC, and NPVF expressing cells were located in the PVN/DMN. KISS1 expression in the caudal-ARC and POA was higher in the late-follicular phase of the cycle (just prior to the GnRH/LH surge) than in the luteal phase. NPVF expression was also higher in the late-follicular phase. We ascertained whether kisspeptin and/or GnIH cells project to GnRH neurons in the primate. Close appositions of kisspeptin and GnIH fibers were found on GnRH neurons, with no change across the menstrual cycle. These data suggest a role for kisspeptin in the stimulation of GnRH cells prior to the preovulatory GnRH/LH surge in non-human primates. The role of GnIH is less clear, with paradoxical up-regulation of gene expression in the late-follicular phase of the menstrual cycle.
Original languageEnglish
Pages (from-to)568 - 577
Number of pages10
JournalBiology of Reproduction
Issue number4
Publication statusPublished - 2010

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