Cross-talk between N-methyl-D-aspartate and adrenergic neurotransmission in the regulation of hypothalamic GnRH gene expression.

Although it has been known that activation of N-methyl-D-aspartate (NMDA) receptor effectively stimulates GnRH biosynthesis and release from the rat hypothalamus, no evidence that NMDA receptors exist in GnRH neurons is yet available. It is then presumed that the action of NMDA on GnRH neurons, may be indirectly mediated through interneurons, such as catecholamines. The present study is designed to investigate whether the effect of NMDA on GnRH gene expression is mediated by adrenergic neuronal system. Adrenergic receptor antagonists were administered 30 min prior to NMDA administration to immature male rats and then animals sacrificed 60 min after NMDA administration. GnRH mRNA levels were determined by Northern blot analysis using a GnRH RNA probe. Inhibition of either alpha 1 adrenergic receptor with prazosin or beta adrenergic receptor with propranolol did not cause any change in the basal GnRH mRNA levels but reduced NMDA-induced GnRH mRNA levels. However, inhibition of alpha 2 adrenergic receptor with yohimbine increased GnRH mRNA levels but did not affect NMDA-induced GnRH mRNA levels. These findings suggest that the effect of NMDA on GnRH gene expression is mediated through adrenergic neurotransmission.