Cross-talk between excitatory and inhibitory amino acids in the regulation of luteinizing hormone-releasing hormone secretion.

Abstract

Inhibitory (IAA) and excitatory amino acid (EAA) neurotransmitters appear to play an important role in regulating reproductive functions. L-Glutamic acid (GLU), the major representative of the EAA system, stimulates LHRH release from arcuate nucleus-median eminence (AN-ME) fragments in vitro. Several studies have provided evidence for considering gamma-aminobutyric acid (GABA), a major IAA neurotransmitter, as another regulator of LHRH secretion. Recent reports have indicated that a cross-talk between GABA and GLU participates in the regulation of synaptic transmission in the brain. In concert with this notion, we present evidence indicating that this cross-talk between GABA and GLU appears to be also involved in neuroendocrinological paradigms. In this respect, bicuculline, a GABA-A receptor antagonist, blocked GLU-evoked LHRH secretion from AN-ME fragments in vitro without affecting basal LHRH release. In addition, activation of GABA-A receptors by muscimol (MUS) stimulated basal LHRH secretion. Interestingly, when MUS and GLU were added together to the incubation medium, an additive, stimulatory effect was observed. These observations clearly indicate that a GABAergic mechanism participates, via GABA-A receptors, in GLU-induced LHRH secretion from terminals of the ME. Furthermore, GABA-B receptors appear to negatively modulate the effects of GLU. Activation of GABA-B receptors by baclofen (BAC) blocked GLU-induced LHRH secretion, while phaclofen, a GABA-B receptor antagonist, reversed this effect. In summary, our data provide evidence for a cross-talk between EAA and IAA systems in the regulation of LHRH release, and, therefore, in the control of gonadal function.