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首页> 外文期刊>Endocrinology >RF9 Excitation of GnRH Neurons Is Dependent Upon Kiss1r in the Adult Male and Female Mouse
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RF9 Excitation of GnRH Neurons Is Dependent Upon Kiss1r in the Adult Male and Female Mouse

机译：GnRH神经元的RF9激发取决于成年雄性和雌性小鼠中的Kiss1r

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摘要

The neuropeptide FF receptor antagonist 1-adamantanecarbonyl-Arg-Phe-NH2 trifluoroacetate salt (RF9) has been found to be a remarkably potent activator of gonadotropin secretion in mammals. However, the mechanism of RF9 action on the reproductive axis is unknown. Using acute brain slice electrophysiology in genetically modified mouse models, we have investigated the possibility that RF9 may activate GnRH neurons. In transgenic GnRH-GFP male and female mice, RF9 was found to exert potent, dose-dependent, stimulatory effects on the firing rate of approximately 70% of GnRH neurons. These effects occurred directly on GnRH neurons and were independent of fast amino acid transmission. To assess RF9's action as an neuropeptide FF receptor antagonist at the GnRH neuron, its ability to antagonize the inhibitory effects of RFamide-related peptide-3 on GnRH neuron firing was examined. RF9 exhibited variable ability to prevent the inhibitory effects of RFamide-related peptide-3 on GnRH neurons. Whole-cell recordings from GnRH neurons showed that RF9 generated an inward current in GnRH neurons reminiscent of that evoked by kisspeptin. We therefore examined RF9 actions in kisspeptin receptor knockout mice. RF9 was found to have no effects at all on GnRH neurons in GnRH-GFP; Kiss1r-null mice, although these cells exhibited normal intrinsic electrical properties and remained responsive to GABA and glutamate. This study reveals that RF9 directly activates GnRH neurons in the mouse and that this is dependent upon Kiss1r expression.
机译：已经发现，神经肽FF受体拮抗剂1-金刚烷羰基-Arg-Phe-NH2三氟乙酸盐（RF9）是哺乳动物中促性腺激素分泌的显着激活剂。但是，RF9作用于生殖轴的机制尚不清楚。在转基因小鼠模型中使用急性脑切片电生理学，我们已经研究了RF9可能激活GnRH神经元的可能性。在转基因的GnRH-GFP雄性和雌性小鼠中，RF9被发现对大约70％的GnRH神经元的放电率产生有效的剂量依赖性刺激作用。这些作用直接发生在GnRH神经元上，与快速氨基酸传递无关。为了评估RF9在GnRH神经元处作为神经肽FF受体拮抗剂的作用，研究了其拮抗RFamide相关肽3对GnRH神经元放电的抑制作用的能力。 RF9表现出可变的能力来阻止RFamide相关肽3对GnRH神经元的抑制作用。 GnRH神经元的全细胞记录显示，RF9在GnRH神经元中产生了内向电流，使人联想到kisspeptin引起的内向电流。因此，我们检查了kisepteptin受体敲除小鼠中的RF9作用。发现RF9对GnRH-GFP中的GnRH神经元完全没有影响。 Kiss1r-null小鼠，尽管这些细胞表现出正常的内在电学性质，并且仍然对GABA和谷氨酸有反应。这项研究表明，RF9直接激活小鼠中的GnRH神经元，这取决于Kiss1r的表达。

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