Localization of GPR54 and gonadotropin-releasing hormone in neurons in the hypothalamus of the dog.

Abstract

The KISS1 gene encodes a family of peptides called kisspeptins, which bind to the G protein coupled receptor GPR54. Dysfunction of GPR54 leads to an insufficient release of gonadotropins and a failure to enter puberty, which implies that KISS1/GPR54 signaling plays an essential role in reproduction. Kisspeptin directly stimulates the release of GnRH from the forebrain after activation of GPR54, which is expressed by GnRH neurons. There are two major hypothalamic kisspeptin populations, with one in the arcuate nucleus (ARC) and one in the preoptic area (POA) or anteroventricular periventricular nucleus (AVPV), depending on the species. KISS1 gene expression is regulated by the presence or absence of sex steroids. Kisspeptin neurons in the ARC have been implicated in mediating the negative feedback of sex steroids on GnRH secretion while the kisspeptin neurons in the POA / AVPV are positively regulated by sex steroids. In other words, ARC kisspeptin neurons are involved in controlling the tonic pulsatile release of GnRH, whereas kisspeptin neurons in the POA / AVPV are responsible for the induction of the pre-ovulatory LH surge. Although KISS1/GPR54 signaling could lead to new therapeutic opportunities such as non-surgical contraception, estrus prevention and ovulation induction, it has not yet been studied in the dog. The aim of this research was to identify the location of GPR54 containing neurons and GnRH neurons in the canine hypothalamus. This report has demonstrated that GnRH neurons and GPR54 containing neurons were present on both sides of the third ventricle in the arcuate nucleus (ARC) region and slightly more dorsal and lateral, which corresponds to the preoptic area (POA) in the hypothalamus of the Beagle bitch and shows theoretical co-localization of GnRH neurons and GPR54 in the ARC and POA, where GnRH neurons and GPR54 were separately detected by immunohistochemistry. Because only one dog was used in this research and the negative controls showed immuno-positive results, the results of this report should be interpreted with caution.