Seong J Y, Lee Y K, Lee C C, Kim K
Department of Molecular Biology, Seoul National University, Korea.
Neuroendocrinology. 1993 Aug;58(2):234-9. doi: 10.1159/000126538.
We previously reported that GnRH gene expression was enhanced by progesterone (P) in the hypothalamus from ovariectomized and estrogen (OVX+E) treated immature rats. Recent studies indicate that excitatory amino 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-induced 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 by Northern blot hybridization using 32P-labeled antisense RNA, and GnRH release in vitro from the hypothalamic fragments was monitored by GnRH 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 indicate that excitatory amino acids by way of NMDA receptor are involved in the transsynaptic regulation of GnRH gene expression.
我们之前报道过，在去卵巢并用雌激素处理的未成熟大鼠（OVX+E）的下丘脑，促性腺激素释放激素（GnRH）基因表达会被孕酮（P）增强。近期研究表明，兴奋性氨基酸可能在类固醇对GnRH分泌和基因表达的调节中发挥重要作用。因此，本研究试图检测兴奋性氨基酸是否参与体外P诱导的GnRH基因表达和释放。给OVX+E+P处理的青春期前雌性大鼠注射NMDA受体拮抗剂MK-801或非NMDA受体拮抗剂CNQX。使用32P标记的反义RNA通过Northern印迹杂交法测定GnRH mRNA，并通过GnRH放射免疫测定法监测下丘脑片段体外GnRH的释放。注射MK-801（0.2mg/kg）2小时可显著降低P诱导的GnRH基因表达和释放，而CNQX（0.4mg/kg）则无此作用。这些结果清楚地表明，通过NMDA受体的兴奋性氨基酸参与了GnRH基因表达的跨突触调节。
