Brain mechanism regulating pulsatile secretion of luteinizing hormone-releasing hormone

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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.