Centre for Neuroendocrinology, Department of Physiology, School of Medical Sciences, University of Otago, Dunedin 9054, New Zealand.
Mol Cell Endocrinol. 2010 Aug 5;324(1-2):45-50. doi: 10.1016/j.mce.2010.01.026. Epub 2010 Jan 28.
Studies undertaken in many species indicate that kisspeptin-Gpr54 signaling is essential for the activation of gonadotropin-releasing hormone (GnRH) neurons to bring about puberty. Investigations in transgenic mouse models, in particular, have highlighted the importance of kisspeptin signaling at the level of the GnRH neuron itself in this process. This review aims to highlight current understanding of the neurobiological mechanisms underlying the kisspeptin activation of postnatal GnRH neurons. The three key features of the kisspeptin-Gpr54-GnRH neuron axis leading up to puberty are (i) the expression of adult-like levels of Gpr54 mRNA in GnRH neurons well in advance of puberty, (ii) a modest increase in the electrical response of GnRH neurons to Gpr54 activation across postnatal development and (iii), the "sudden" appearance of kisspeptin fibers surrounding GnRH neuron cell bodies/proximal dendrites just prior to puberty onset. These kisspeptin fibers are likely to originate from the kisspeptin population located in the rostral periventricular region of the third ventricle (RP3V). Together, available data suggest that the key step in the kisspeptin control of puberty lies in the control of kisspeptin synthesis within RP3V kisspeptin neurons that innervate GnRH neurons. This has recently been shown to be dependent upon circulating estradiol concentrations. As such, we propose that RP3V kisspeptin neurons represent a critical estradiol-dependent amplification mechanism brought into play relatively late in pubertal development to activate GnRH neurons and complete the process of puberty onset. Subsequently, in the adult female, this same circuitry is used to activate GnRH neurons to generate the cyclical preovulatory GnRH/LH surge.
许多物种的研究表明， kisspeptin-Gpr54 信号对于促性腺激素释放激素 (GnRH) 神经元的激活以实现青春期至关重要。特别是在转基因小鼠模型中的研究强调了 kisspeptin 信号在 GnRH 神经元本身水平上在这个过程中的重要性。本综述旨在强调目前对 kisspeptin 激活产后 GnRH 神经元的神经生物学机制的理解。导致青春期的 kisspeptin-Gpr54-GnRH 神经元轴的三个关键特征是：(i) GnRH 神经元中 Gpr54 mRNA 的表达水平与成年相似，远早于青春期；(ii) GnRH 神经元对 Gpr54 激活的电反应在产后发育过程中适度增加；以及 (iii)，在青春期开始之前，刚好在 GnRH 神经元胞体/近端树突周围出现 kisspeptin 纤维。这些 kisspeptin 纤维可能源自位于第三脑室 (RP3V) 头侧室旁区的 kisspeptin 群体。综上所述，现有数据表明，kisspeptin 控制青春期的关键步骤在于控制支配 GnRH 神经元的 RP3V kisspeptin 神经元中的 kisspeptin 合成。最近的研究表明，这取决于循环中的雌二醇浓度。因此，我们提出 RP3V kisspeptin 神经元代表了一个关键的雌二醇依赖性放大机制，在青春期发育后期被激活，以激活 GnRH 神经元并完成青春期启动过程。随后，在成年女性中，相同的回路被用于激活 GnRH 神经元以产生周期性的促性腺激素释放激素/LH 激增。
