Kisspeptin regulation of arcuate neuron excitability in kisspeptin receptor knockout mice

Endocrinology
Xinhuai Liu, Allan E Herbison

Abstract

The G protein-coupled receptor 54 (GPR54) is critical for kisspeptin to activate GnRH neurons to modulate fertility. However, the often mismatching distribution of kisspeptin and GPR54 in the brain suggests that kisspeptin may also act on other receptors. The arcuate nucleus (ARN) is one brain region with a very high density of kisspeptin fibers but only limited evidence for the expression of GPR54. Using acute brain slice electrophysiology in combination with Gpr54 knockout (GPR54KO) mouse models, we examined whether actions of kisspeptin in the ARN were dependent upon GPR54. Cell-attached recordings from unidentified ARN neurons in wild-type mice revealed that approximately one third of neurons were either excited or inhibited by kisspeptin in a dose-dependent manner. The responses of ARN neurons to kisspeptin were exactly the same in GPR54KO mice despite effects of kisspeptin on GnRH neurons being abolished. To evaluate whether kisspeptin may be acting through neuropeptide FF receptors, the effects of an agonist RFamide-related peptide 3 (RFRP-3) and antagonists RF9 and BIBP-3226 were evaluated. Both the excitatory and inhibitory effects of kisspeptin were mimicked by the agonist RFRP-3. RF9 itself activated ARN neurons and ...Continue Reading

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Citations

Sep 29, 2015·Trends in Endocrinology and Metabolism : TEM·Mehboob A HussainAndrew Wolfe
Jul 9, 2016·Current Opinion in Pediatrics·Sarantis Livadas, George P Chrousos
Jun 2, 2016·Scientific Reports·C DecourtM Beltramo
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Jun 2, 2016·Endocrinology and Metabolism·Xinhuai Liu, Allan E Herbison
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Dec 5, 2020·Nature Reviews. Endocrinology·Edouard G MillsWaljit S Dhillo
May 9, 2021·Molecular and Cellular Endocrinology·Virginia DelliKonstantina Chachlaki

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