Brain mechanism regulating pulsatile secretion of luteinizing hormone-releasing hormone

我们提出假设，LHRH脉冲发生器由非LHRH神经元组成，位于MBH。LHRH脉冲发生器作用LHRH神经元的位置可能是LHRH神经元终末集中的正中隆起，因为完全去传入将LHRH神经元终末与位于视前/隔区的细胞体分开，不会损害脉动性黄体生成素的分泌。为了探索这种可能性，我们从去卵巢大鼠的正中隆起组织中体外检测了LHRH的释放，并与不同的神经递质孵育，如单胺或兴奋性氨基酸(EaaS)。任何单胺，如去甲肾上腺素、多巴胺、5-羟色胺或组胺，在生理剂量下都不能在体外诱导正中隆起组织释放LHRH。另一方面，谷氨酸、NMDA、AMPA或海人藻酸等EAA激动剂在体外可增加组织中LHRH的释放，提示内源性EaAs释放到正中隆起产生了搏动性的LHRH释放。然后，我们试图通过在正中隆起植入兴奋性氨基酸拮抗剂来阻断黄体生成素脉冲，以测试内源性EaAs是否参与了正中隆起产生搏动性LHRH释放。NMDA型EAA受体拮抗剂CPP和非NMDA型受体拮抗剂DNQX均能有效抑制搏动性黄体生成素的分泌，但抑制作用不完全。目前的结果支持我们的假设，即LHRH的脉动性释放可能是通过EAA受体在正中隆起的LHRH神经元终末调节的。

We proposed hypothesis that the LHRH pulse generator consists of non-LHRH neurons and is located in the MBH.The site at which the LHRH pulse generator acts LHRH neurons could be the median eminence where the terminals of LHRH neurons are concentrated, because pulsatile LH secretion was not impaired by the complete deafferentation which separated the LHRH neuronal terminals from the cell bodies located in the preoptic / septum region. To explore this possibility, we examined in vitro LHRH release from the median eminence tissues taken from ovariectomized rates and incubated with various neurotransmitters, such as monoamines or excitatory amino acids (EAAs). Any monoamines, such as norepinephrine, dopamine, serotonin or histamine, did not induce in vitro LHRH release from the median eminence tissues at a physiological dose. On the other hand, EAA agonists, such as glutamate, NMDA, AMPA or kainate, increased in vitro LHRH release from the tissues, suggesting that the endogenous EAAs released into the median eminence generate the pulsatile LHRH release. We then tried to block LH pulses by implanting excitatory amino acid antagonists into the median eminence to test whether the endogenous EAAs are involved in generating pulsatile LHRH release at the median eminence. Both CPP, a NMDA-type EAA receptor antagonist, and DNQX, a non-NMDA-type receptor antagonist, were effective in decreasing pulsatile LH secretion, although the suppression was not complete. The present results strongy support our hypothesis that pulsatile LHRH release is regulated at the LHRH neuronal terminals located in the median eminence probably through EAA receptors.