Urbanski H F, Fahy M M, Daschel M, Meshul C
Division of Neuroscience, Oregon Regional Primate Research Center, Beaverton 97006.
J Reprod Fertil. 1994 Jan;100(1):5-9. doi: 10.1530/jrf.0.1000005.
Although the excitatory amino acid (EAA) receptor agonist N-methyl-D-aspartate (NMDA) can exert profound stimulatory effects on the neuroendocrine reproductive axis of Syrian hamsters, the exact relationship between NMDA receptors and LHRH neurones is unclear. In the present study, in situ hybridization histochemistry was performed on sections of hamster brain using an 35S-labelled riboprobe to the EAA receptor gene, NMDAR1. A high content of NMDA receptor mRNA was detected not only in brain areas classically associated with specific NMDA binding (for example, hippocampus and cerebral cortex) but also in the hypothalamus, in particular the ventromedial-arcuate area; diffuse hybridization of the riboprobe also occurred in the medial-septal area and diagonal band of Broca, regions of the hamster brain in which the LHRH neuronal perikarya are primarily located. In a separate experiment, RNA was extracted from immortalized LHRH neurones (GT1-1 and GT1-7 cells) and used for northern analysis with a 32P-labelled NMDAR1 riboprobe. Clear-cut hybridization occurred with RNA bands of approximately 4.2 and 4.4 kb from the two LHRH neuronal subtypes. These findings suggest that at least some of the stimulatory action of EAAs on LHRH secretion is likely to be exerted directly at the level of the LHRH neurones rather than being mediated through interneurones. Furthermore, the demonstration of abundant NMDA receptor gene expression within hypothalamic areas that lie outside the blood-brain barrier adds plausibility to the concern that EAAs of dietary origin, such as monosodium glutamate, have the capacity to perturb the normal secretory activity of neuroendocrine circuits of the hypothalamus.
尽管兴奋性氨基酸（EAA）受体激动剂N-甲基-D-天冬氨酸（NMDA）可对叙利亚仓鼠的神经内分泌生殖轴产生深远的刺激作用，但NMDA受体与促性腺激素释放激素（LHRH）神经元之间的确切关系尚不清楚。在本研究中，使用针对EAA受体基因NMDAR1的35S标记核糖探针，对仓鼠脑切片进行了原位杂交组织化学分析。不仅在经典上与特定NMDA结合相关的脑区（例如海马体和大脑皮层）中检测到高含量的NMDA受体mRNA，在下丘脑中也检测到，特别是腹内侧-弓状区域；核糖探针在中隔内侧区域和布罗卡斜带中也出现了弥漫性杂交，仓鼠脑中LHRH神经元胞体主要位于这些区域。在另一项实验中，从永生化的LHRH神经元（GT1-1和GT1-7细胞）中提取RNA，并使用32P标记的NMDAR1核糖探针进行Northern分析。来自两种LHRH神经元亚型的约4.2和4.4 kb的RNA条带出现了清晰的杂交信号。这些发现表明，EAA对LHRH分泌的至少部分刺激作用可能直接在LHRH神经元水平上发挥，而不是通过中间神经元介导。此外，在血脑屏障之外的下丘脑区域内大量NMDA受体基因表达的证明，增加了人们对饮食来源的EAA（如谷氨酸钠）有能力扰乱下丘脑神经内分泌回路正常分泌活动这一担忧的合理性。
