NITRIC-OXIDE REGULATES LUTEINIZING-HORMONE-RELEASING HORMONE-SECRETION

We have analyzed the role of nitric oxide (NO), an unorthodox and nove l neuromodulator, on luteinizing hormone-releasing hormone (LHRH) secr etion. Sodium nitroprusside (SNP), an NO donor, was used to challenge LHRH neurons using both hypothalamic explants and an immortalized neur onal cell line (GTI cells) in vitro. In both paradigms, SNPwas 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 cGM P levels. In addition, exposure of LHRH cells (GTI -7 cells) to increa sing concentrations of a soluble analog of cGMP (8-Br-cGMP) enhanced L HRH release in a dose-dependent manner, indicating that LHRH neurons h ave the intrinsic ability to respond to the intracellular messenger el icited by NO,i.e.,cGMP. Furthermore, sodium nitroprusside-induced LHRH secretion from GTI-7 cells was blocked, in a dose-dependent manner, b y Rp-8-Br-cGMPS, a cGMP analog which blocks cGMP-dependent protein kin ase. 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, th ereby, reproductive functions.