Characterization of Kiss1r (Gpr54)-expressing neurons in the arcuate nucleus of the female rat hypothalamus

Abstract

Kisspeptin is essential in reproduction, and acts by stimulating neurons expressing gonadotropin-releasing hormone (GnRH). Recent studies suggest that kisspeptin has multiple roles in the modulation of neuronal circuits in systems outside the hypothalamic-pituitary-gonadal axis. Our recent research using in situ hybridization (ISH) clarified the histological distribution of Kiss1r (Gpr54)-expressing neurons in the rat brain which were presumed to be putative targets of kisspeptin. The arcuate nucleus (ARN) of the hypothalamus is one of the brain regions in which Kiss1r expression in non-GnRH neurons is prominent. However, characteristics of Kiss1r-expressing neurons in the ARN remain unclear. The aim of the present study was to determine the neurochemical characteristics of Kiss1r-expressing neurons in the ARN using ISH and immunofluorescence. We revealed that the majority (approximately 63%) of Kiss1r-expressing neurons in the ARN were proopiomelanocortin (POMC) neurons, which have an anorexic effect in mammals. Additionally, a few Kiss1r-expressing neurons in the dorsal ARN are tuberoinfundibular dopamine (TIDA) neurons, which control milk production by inhibiting prolactin secretion from the anterior pituitary. TIDA neurons showed relatively weak Kiss1r ISH signal compared with POMC neurons, and low co-expression of Kiss1r (approximately 15%). We also examined the expression of Kiss1r in neuropeptide Y and kisspeptin neurons, which are reported to arise from POMC-expressing progenitor cells during development. However, the vast majority of neuropeptide Y and kisspeptin neurons in the ARN did not express Kiss1r. These results suggest the possibility that kisspeptin may directly regulate energy homeostasis and milk production by modulating the activity of POMC and TIDA neurons, respectively. Our results provide an insight into the wide variety of roles kisspeptin plays in homeostatic and neuroendocrine functions.

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