Centre for Neuroendocrinology and Department of Physiology, University of Otago School of Medical Sciences, Dunedin 9054, New Zealand.
Nat Rev Endocrinol. 2016 Aug;12(8):452-66. doi: 10.1038/nrendo.2016.70. Epub 2016 May 20.
The gonadotropin-releasing hormone (GnRH) neuronal network generates pulse and surge modes of gonadotropin secretion critical for puberty and fertility. The arcuate nucleus kisspeptin neurons that innervate the projections of GnRH neurons in and around their neurosecretory zone are key components of the pulse generator in all mammals. By contrast, kisspeptin neurons located in the preoptic area project to GnRH neuron cell bodies and proximal dendrites and are involved in surge generation in female rodents (and possibly other species). The hypothalamic-pituitary-gonadal axis develops embryonically but, apart from short periods of activation immediately after birth, remains suppressed through a combination of gonadal and non-gonadal mechanisms. At puberty onset, the pulse generator reactivates, probably owing to progressive stimulatory influences on GnRH neurons from glial and neurotransmitter signalling, and the re-emergence of stimulatory arcuate kisspeptin input. In females, the development of pulsatile gonadotropin secretion enables final maturation of the surge generator that ultimately triggers the first ovulation. Representation of the GnRH neuronal network as a series of interlocking functional modules could help conceptualization of its functioning in different species. Insights into pulse and surge generation are expected to aid development of therapeutic strategies ameliorating pubertal disorders and infertility in the clinic.
促性腺激素释放激素（GnRH）神经元网络产生促性腺激素分泌的脉冲和涌动模式，这对青春期和生育能力至关重要。支配 GnRH 神经元投射的弓状核 kisspeptin 神经元是所有哺乳动物脉冲发生器的关键组成部分。相比之下，位于视前区的 kisspeptin 神经元投射到 GnRH 神经元的胞体和近端树突，并参与雌性啮齿动物（可能还有其他物种）的涌动生成。下丘脑-垂体-性腺轴在胚胎发育过程中发育，但除了出生后立即短暂激活外，通过性腺和非性腺机制的结合仍然受到抑制。在青春期开始时，脉冲发生器重新激活，可能是由于胶质细胞和神经递质信号对 GnRH 神经元的逐渐刺激，以及刺激性弓状 kisspeptin 输入的重新出现。在女性中，促性腺激素分泌的脉冲性发育使涌动发生器最终成熟，最终引发第一次排卵。将 GnRH 神经元网络表示为一系列相互关联的功能模块可以帮助理解其在不同物种中的功能。对脉冲和涌动产生的深入了解有望有助于开发治疗策略，改善临床青春期障碍和不孕不育。
