Moretto M, López F J, Negro-Vilar A
Reproductive Neuroendocrinology Section, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Endocrinology. 1993 Nov;133(5):2399-402. doi: 10.1210/endo.133.5.8104781.
We have analyzed the role of nitric oxide (NO), an unorthodox and novel neuromodulator, on luteinizing hormone-releasing hormone (LHRH) secretion. Sodium nitroprusside (SNP), an NO donor, was used to challenge LHRH neurons using both hypothalamic explants and an immortalized neuronal cell line (GT1 cells) in vitro. In both paradigms, SNP was able to stimulate LHRH release in a dose-dependent manner. This action of SNP was accompanied by an elevation in both extra- and intra-cellular cGMP levels. In addition, exposure of LHRH cells (GT1-7 cells) to increasing concentrations of a soluble analog of cGMP (8-Br-cGMP) enhanced LHRH release in a dose-dependent manner, indicating that LHRH neurons have the intrinsic ability to respond to the intracellular messenger elicited by NO, i.e., cGMP. Furthermore, sodium nitroprusside-induced LHRH secretion from GT1-7 cells was blocked, in a dose-dependent manner, by Rp-8-Br-cGMPS, a cGMP analog which blocks cGMP-dependent protein kinase. These data clearly demonstrate that NO stimulates LHRH secretion by activating guanylate cyclase, and support a potential role of NO as a neuroactive agent involved in the control of LHRH secretion and, thereby, reproductive functions.
我们分析了一氧化氮（NO）这种非传统新型神经调节剂对促黄体生成素释放激素（LHRH）分泌的作用。使用一氧化氮供体硝普钠（SNP），通过体外下丘脑外植体和永生化神经元细胞系（GT1细胞）对LHRH神经元进行刺激。在这两种实验模式中，SNP均能以剂量依赖的方式刺激LHRH释放。SNP的这一作用伴随着细胞外和细胞内cGMP水平的升高。此外，将LHRH细胞（GT1-7细胞）暴露于浓度递增的可溶性cGMP类似物（8-溴-cGMP）中，LHRH释放以剂量依赖的方式增强，这表明LHRH神经元具有对由NO引发的细胞内信使即cGMP作出反应的内在能力。此外，硝普钠诱导的GT1-7细胞LHRH分泌被Rp-8-溴-cGMPS以剂量依赖的方式阻断，Rp-8-溴-cGMPS是一种可阻断cGMP依赖性蛋白激酶的cGMP类似物。这些数据清楚地表明，NO通过激活鸟苷酸环化酶刺激LHRH分泌，并支持NO作为一种神经活性物质在控制LHRH分泌进而调节生殖功能中发挥潜在作用。
