Centre for Neuroendocrinology and Department of Physiology, University of Otago School of Biomedical Sciences, Dunedin, New Zealand.
Endocrinology. 2021 Mar 1;162(3). doi: 10.1210/endocr/bqaa237.
Acute stress is a potent suppressor of pulsatile luteinizing hormone (LH) secretion, but the mechanisms through which corticotrophin-releasing hormone (CRH) neurons inhibit gonadotropin-releasing hormone (GnRH) release remain unclear. The activation of paraventricular nucleus (PVN) CRH neurons with Cre-dependent hM3Dq in Crh-Cre female mice resulted in the robust suppression of pulsatile LH secretion. Channelrhodopsin (ChR2)-assisted circuit mapping revealed that PVN CRH neuron projections existed around kisspeptin neurons in the arcuate nucleus (ARN) although many more fibers made close appositions with GnRH neuron distal dendrons in the ventral ARN. Acutely prepared brain slice electrophysiology experiments in GnRH- green fluorescent protein (GFP) mice showed a dose-dependent (30 and 300 nM CRH) activation of firing in ~20% of GnRH neurons in both intact diestrus and ovariectomized mice with inhibitory effects being uncommon (<8%). Confocal GCaMP6 imaging of GnRH neuron distal dendrons in acute para-horizontal brain slices from GnRH-Cre mice injected with Cre-dependent GCaMP6s adeno-associated viruses demonstrated no effects of 30 to 300 nM CRH on GnRH neuron dendron calcium concentrations. Electrophysiological recordings of ARN kisspeptin neurons in Crh-Cre,Kiss1-GFP mice revealed no effects of 30 -300 nM CRH on basal or neurokinin B-stimulated firing rate. Similarly, the optogenetic activation (2-20 Hz) of CRH nerve terminals in the ARN of Crh-Cre,Kiss1-GFP mice injected with Cre-dependent ChR2 had no effect on kisspeptin neuron firing. Together, these studies demonstrate that PVN CRH neurons potently suppress LH pulsatility but do not exert direct inhibitory control over GnRH neurons, at their cell body or dendron, or the ARN kisspeptin neuron pulse generator in the female mouse.
急性应激强烈抑制促黄体生成激素（LH）脉冲分泌，但促肾上腺皮质释放激素（CRH）神经元抑制促性腺激素释放激素（GnRH）释放的机制尚不清楚。在 Crh-Cre 雌性小鼠中，使用 Cre 依赖性 hM3Dq 激活室旁核（PVN）CRH 神经元，导致 LH 脉冲分泌的强烈抑制。通过通道视紫红质（ChR2）辅助的回路映射显示，PVN CRH 神经元投射存在于弓状核（ARN）中的 kisspeptin 神经元周围，尽管更多的纤维与 GnRH 神经元远端树突在 ARN 腹侧形成紧密贴合。在 GnRH-绿色荧光蛋白（GFP）小鼠的急性脑切片电生理学实验中，发现 30 和 300 nM CRH 对完整动情间期和去卵巢小鼠中约 20%的 GnRH 神经元的放电有剂量依赖性激活，抑制作用不常见（<8%）。用 Cre 依赖性 GCaMP6s 腺相关病毒注射 GnRH-Cre 小鼠的急性水平脑切片中的 GnRH 神经元远端树突的共聚焦 GCaMP6 成像显示，30 至 300 nM CRH 对 GnRH 神经元树突钙浓度无影响。在 Crh-Cre，Kiss1-GFP 小鼠的 ARN kisspeptin 神经元的电生理记录中，发现 30-300 nM CRH 对基础或神经激肽 B 刺激的放电率没有影响。同样，在注射了 Cre 依赖性 ChR2 的 Crh-Cre，Kiss1-GFP 小鼠的 ARN 中，CRH 神经末梢的光遗传学激活（2-20 Hz）对 kisspeptin 神经元的放电也没有影响。综上所述，这些研究表明，PVN CRH 神经元强烈抑制 LH 脉冲性，但对 GnRH 神经元、其胞体或树突，或雌性小鼠 ARN kisspeptin 神经元脉冲发生器没有直接的抑制控制作用。
