N-METHYL-D-ASPARTATE (NMDA) STIMULATES LHRH RELEASE VIA THE NMDA RECEPTOR IN AN LHRH NEURONAL CELL LINE (GT1-1)

Abstract

Previous studies demonstrated that an excitatory amino acid analog, NMDA, stimulates LHRH secretion in the ovine fetus, prepubertal primate and rat at the hypothalamic level. It is not known if this stimulatory effect of NMDA is mediated directly on the LHRH neurosecretory neuron. A hypothalamic LHRH neuronal cell line (GT1-1) was used to study the effect of NMDA on LHRH release by both superfusion and static incubation with glycine enriched media. Studies with GT1-1 cells indicate that LHRH neurons exhibit spontaneous autorhythmicity and function intrinsically as a neuronal oscillator for the synchronous discharge of LHRH pulses. Superfusion of GT1- cells after a 90 min control period with a 10 min pulse of NMDA (10−4 - 10−2 M) alternating with 10 min of media alone for 90 min increased LHRH pulse amplitude by 35-50% (p<0.05) but had no effect on the interpulse interval (≈18 min by “Cluster”). In static incubations, NMDA (10−4 - 10−2 M) increased LHRH release while 5x10−2 M NMDA had no effect. A competitive NMDA antagonist, AP5 (10−3 - 10−2 M) inhibited the action of NMDA.