NMDA RECEPTOR ANTAGONIST DECREASES THE PROGESTERONE-INDUCED INCREASE IN GNRH GENE-EXPRESSION IN THE RAT HYPOTHALAMUS

We previously reported that GnRH gene expression was enhanced by proge sterone (P) in the hypothalamus from ovariectomized and estrogen (OVXE) treated immature rats. Recent studies indicate that excitatory amin o acids may play an important role in the regulation of GnRH secretion and gene expression by steroids. Therefore the present study attempts to examine whether excitatory amino acids are involved in the P-induc ed GnRH gene expression and release in vitro. MK-801, an NMDA receptor antagonist or CNQX, a non-NMDA receptor antagonist, was administered to OVX+E+P-treated prepubertal female rats. GnRH mRNA was determined b y Northern blot hybridization using P-32-labeled antisense RNA, and Gn RH release in vitro from the hypothalamic fragments was monitored by G nRH radioimmunoassay. The administration of MK-801 (0.2 mg/kg) for 2 h significantly reduced the P-induced GnRH gene expression and release, whereas CNQX (0.4 mg/kg) had no effect. These results clearly indicat e that excitatory amino acids by way of NMDA receptor are involved in the transsynaptic regulation of GnRH gene expression.