Neural Determinants of Pulsatile Luteinizing Hormone Secretion in Male Mice
Neural Determinants of Pulsatile Luteinizing Hormone Secretion in Male Mice
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DOI：
10.1210/endocr/bqz045
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发表时间：
2020-02-01
期刊：
影响因子：
4.8
通讯作者：
Herbison, Allan E.
中科院分区：
文献类型：
--
作者：
Han, Su Young;Cheong, Isaiah;Herbison, Allan E.
促性腺激素释放激素（GnRH）脉冲发生器驱动脉冲式促黄体生成激素（LH）分泌，这对生育至关重要。然而，脉冲发生器操作以驱动有效LH脉动性的约束仍然不清楚。我们使用光遗传学激活的弓状核kisspeptin神经元，最近被确定为GnRH脉冲发生器，以评估不同的脉冲发生器频率在驱动脉冲LH分泌在完整的自由行为的雄性小鼠的效率。以45分钟间隔激活脉冲发生器产生的LH脉冲与在完整雄性小鼠中观察到的类似，而9分钟间隔刺激产生的LH曲线与性腺切除（GDX）雄性小鼠无区别。然而，更频繁地激活脉冲发生器导致LH分泌紊乱。直接激活GnRH神经元远端投射的光遗传学实验给出了完全相同的结果，表明垂体是高频解码的场所。为了评估脉冲发生器的状态依赖性行为，在GDX和完整小鼠中比较弓状kisspeptin神经元的高频激活的效果。同样的刺激导致GDX小鼠LH释放的总体抑制，但在完整的男性刺激。这些研究表明，GnRH脉冲发生器是LH脉冲分布的主要决定因素，脉冲发生器频率和LH脉冲频率之间存在非线性关系。这可能是脉冲发生器的刺激输入对完整和GDX动物LH分泌产生相反影响的能力的基础。
The gonadotrophin-releasing hormone (GnRH) pulse generator drives pulsatile luteinizing hormone (LH) secretion essential for fertility. However, the constraints within which the pulse generator operates to drive efficient LH pulsatility remain unclear. We used optogenetic activation of the arcuate nucleus kisspeptin neurons, recently identified as the GnRH pulse generator, to assess the efficiency of different pulse generator frequencies in driving pulsatile LH secretion in intact freely behaving male mice. Activating the pulse generator at 45-minute intervals generated LH pulses similar to those observed in intact male mice while 9-minute interval stimulation generated LH profiles indistinguishable from gonadectomized (GDX) male mice. However, more frequent activation of the pulse generator resulted in disordered LH secretion. Optogenetic experiments directly activating the distal projections of the GnRH neuron gave the exact same results, indicating the pituitary to be the locus of the high frequency decoding. To evaluate the state-dependent behavior of the pulse generator, the effects of high-frequency activation of the arcuate kisspeptin neurons were compared in GDX and intact mice. The same stimulus resulted in an overall inhibition of LH release in GDX mice but stimulation in intact males. These studies demonstrate that the GnRH pulse generator is the primary determinant of LH pulse profile and that a nonlinear relationship exists between pulse generator frequency and LH pulse frequency. This may underlie the ability of stimulatory inputs to the pulse generator to have opposite effects on LH secretion in intact and GDX animals.