Characterisation of Kiss1r (Gpr54)‐Expressing Neurones in the Arcuate Nucleus of the Female Rat Hypothalamus

Abstract

Kisspeptin is essential in reproduction and acts by stimulating neurones expressing gonadotrophin-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 hybridisation (ISH) clarified the histological distribution of Kiss1r (Gpr54)-expressing neurones in the rat brain that 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 neurones is prominent. However, the characteristics of Kiss1r-expressing neurones in the ARN remain unclear. The present study aimed to determine the neurochemical characteristics of Kiss1r-expressing neurones in the ARN using ISH and immunofluorescence. We revealed that the majority (approximately 63%) of Kiss1r-expressing neurones in the ARN were pro-opiomelanocortin (POMC) neurones, which have an anorexic effect in mammals. Additionally, a few Kiss1r-expressing neurones in the dorsal ARN are tuberoinfundibular dopamine (TIDA) neurones, which control milk production by inhibiting prolactin secretion from the anterior pituitary. TIDA neurones showed a relatively weak Kiss1r ISH signal compared to POMC neurones, as well as low co-expression of Kiss1r (approximately 15%). We also examined the expression of Kiss1r in neuropeptide Y and kisspeptin neurones, which are reported to arise from POMC-expressing progenitor cells during development. However, the vast majority of neuropeptide Y and kisspeptin neurones in the ARN did not express Kiss1r. These results suggest that kisspeptin may directly regulate energy homeostasis and milk production by modulating the activity of POMC and TIDA neurones, respectively. Our results provide an insight into the wide variety of roles that kisspeptin plays in homeostatic and neuroendocrine functions.

Kisspeptin and RFRP3 modulate body mass in Phodopus sungorus via two different neuroendocrine pathways

“…Chronic Kp10 increased Pomc and Npy in males, but not in females, which could explain why only male hamsters modified their metabolic phenotype. POMC neurones receive a dense Kp innervation and express Kiss1r in rats, they are directly activated by Kp in mice and they are regulated by a central Kp10 injection in jerboas, altogether supporting a direct effect of Kp on POMC neurones. On the other hand, castration completely abolished the effect of Kp10 on body weight and, because testosterone is known to regulate Pomc and Npy, probably also part of the Kp effect on the metabolic genes is testosterone‐dependent.…”

Kisspeptin and Prolactin

“…122 We have further investigated this question using whole-cell patch clamp recordings in juvenile male rats, and we found no direct effect of kisspeptin-10 on the electrical activity of TIDA neurons. Similarly, others have reported that only a few TIDA neurons express Kiss1r in the female rat, 126 suggesting that Kiss1r does not play a significant role in this neuronal population.…”

Co‐expression of the calcitonin receptor gene in the hypothalamic kisspeptin neurons in female rats

“…Thus, it is speculated that calcitonin and/or amylin could affect the tubuloinfundibular dopaminergic (TIDA) neurons, which in turn, might contribute to controlling prolactin release from the anterior pituitary during lactation. Interestingly, GPR54 expression was evident in the TIDA neurons in rats, suggesting that ARC kisspeptin and TIDA neurons could interact with each other through kisspeptin and CALCR signaling. Furthermore, the Calcr‐ expressing cells in the brain regions close to the cerebral ventricles might have a role as an interface of peripheral and central interaction.…”

“…Interestingly, GPR54 expression was evident in the TIDA neurons in rats, 43 suggesting that ARC kisspeptin and TIDA neurons could interact with each other through kisspeptin and CALCR signaling.…”