Excitatory amino acids constitute a novel class of neurotransmitters, glutamate and aspartate being the most representative transmitters of the family. These substances can also induce extensive neuronal injuries, and can therefore act as excitotoxins. In addition to the toxic effects of these agents, they also exist in physiological conditions in the nervous system and, therefore, may contribute to the control of physiological events. Recently, we characterized the pharmacological profile of glutamate receptors in the hypothalamus in terms of the ability of glutamate to induce LHRH release. We established a dose-response relationship between glutamate and LHRH release from arcuate nucleus-median eminence terminals in vitro. In these studies, we demonstrated that glutamate-induced LHRH release was mainly mediated through kainate-quisqualate receptor type. These observations led us to postulate that excitatory amino acid neurotransmission may be an important input in regulating LHRH release. Studies from other laboratories have indicated that endogenous excitatory amino acid administration or the blockade of endogenous amino acid neurotransmission may alter the onset of puberty in both monkeys and rats. Prompted by our observation of the importance of kainate-quisqualate receptors in the control of LHRH secretion and also by the availability of specific EAA receptor blockers, we initiated a series of studies in order to characterize the role of endogenous amino acids in the control of some physiological events. In an initial study, we observed that both a competitive NMDA receptor antagonist, AP7, and a competitive non-NMDA receptor antagonist, DNQX, were able to block, when administered into the third ventricle, the estradiol-induced LH surge in ovariectomized female rats. This provided evidence for a role of endogenous excitatory amino acids in a well characterized classic endocrine model. These and ongoing studies on the spontaneously occurring proestrus LH surge should help to establish a role for the endogenous excitatory neurotransmitters in reproductive physiology.
