Hessler Sabine, Liu Xinhuai, Herbison Allan E
Centre for Neuroendocrinology and Department of Physiology, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand.
J Neuroendocrinol. 2020 May;32(5):e12849. doi: 10.1111/jne.12849. Epub 2020 Apr 26.
Adverse energy states exert a potent suppressive influence on the reproductive axis by inhibiting the pulsatile release of gonadotrophin-releasing hormone and luteinising hormone. One potential mechanism underlying this involves the metabolic-sensing pro-opiomelanocortin and agouti-related peptide/neuropeptide Y (AgRP/NPY) neuronal populations directly controlling the activity of the arcuate nucleus kisspeptin neurones comprising the gonadotrophin-releasing hormone pulse generator. Using acute brain slice electrophysiology and calcium imaging approaches in Kiss1-GFP and Kiss1-GCaMP6 mice, we investigated whether NPY and α-melanocyte-stimulating hormone provide a direct modulatory influence on the activity of arcuate kisspeptin neurones in the adult mouse. NPY was found to exert a potent suppressive influence upon the neurokinin B-evoked firing of approximately one-half of arcuate kisspeptin neurones in both sexes. This effect was blocked partially by the NPY1R antagonist BIBO 3304, whereas the NPY5R antagonist L152,804 was ineffective. NPY also suppressed the neurokinin B-evoked increase in intracellular calcium levels in the presence of tetrodotoxin and amino acid receptor antagonists, indicating that the inhibitory effects of NPY are direct on kisspeptin neurones. By contrast, no effects of α-melanocyte-stimulating hormone were found on the excitability of arcuate kisspeptin neurones. These studies provide further evidence supporting the hypothesis that AgRP/NPY neurones link energy status and luteinising hormone pulsatility by demonstrating that NPY has a direct suppressive influence upon the activity of a subpopulation of arcuate kisspeptin neurones.
不良能量状态通过抑制促性腺激素释放激素和促黄体生成素的脉冲式释放，对生殖轴产生强大的抑制作用。其潜在机制之一涉及代谢感应的阿黑皮素原和刺鼠相关肽/神经肽Y（AgRP/NPY）神经元群体，它们直接控制着构成促性腺激素释放激素脉冲发生器的弓状核吻素神经元的活动。利用Kiss1-GFP和Kiss1-GCaMP6小鼠的急性脑片电生理学和钙成像方法，我们研究了NPY和α-黑素细胞刺激素是否对成年小鼠弓状核吻素神经元的活动提供直接的调节影响。研究发现，NPY对两性中约一半的弓状核吻素神经元的神经激肽B诱发的放电有强大的抑制作用。NPY1R拮抗剂BIBO 3304可部分阻断这种作用，而NPY5R拮抗剂L152,804则无效。在存在河豚毒素和氨基酸受体拮抗剂的情况下，NPY还抑制了神经激肽B诱发的细胞内钙水平的升高，这表明NPY对吻素神经元的抑制作用是直接的。相比之下，未发现α-黑素细胞刺激素对弓状核吻素神经元的兴奋性有影响。这些研究通过证明NPY对弓状核吻素神经元亚群的活动有直接抑制作用，为AgRP/NPY神经元将能量状态与促黄体生成素脉冲性联系起来的假说提供了进一步的证据。
