<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="6.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Sasson, Ravid</style></author><author><style face="normal" font="default" size="100%">Dearth, Robert K</style></author><author><style face="normal" font="default" size="100%">White, Rachel S</style></author><author><style face="normal" font="default" size="100%">Chappell, Patrick E</style></author><author><style face="normal" font="default" size="100%">Mellon, Pamela L</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Orexin A induces GnRH gene expression and secretion from GT1-7 hypothalamic GnRH neurons.</style></title><secondary-title><style face="normal" font="default" size="100%">Neuroendocrinology</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Neuroendocrinology</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Cells, Cultured</style></keyword><keyword><style  face="normal" font="default" size="100%">Cyclic AMP-Dependent Protein Kinases</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Expression Regulation</style></keyword><keyword><style  face="normal" font="default" size="100%">Gonadotropin-Releasing Hormone</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Hypothalamus</style></keyword><keyword><style  face="normal" font="default" size="100%">Intracellular Signaling Peptides and Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice, Inbred C57BL</style></keyword><keyword><style  face="normal" font="default" size="100%">Mitogen-Activated Protein Kinase Kinases</style></keyword><keyword><style  face="normal" font="default" size="100%">Neurons</style></keyword><keyword><style  face="normal" font="default" size="100%">Neuropeptides</style></keyword><keyword><style  face="normal" font="default" size="100%">Neurotransmitter Agents</style></keyword><keyword><style  face="normal" font="default" size="100%">Protein Kinase C</style></keyword><keyword><style  face="normal" font="default" size="100%">Receptors, G-Protein-Coupled</style></keyword><keyword><style  face="normal" font="default" size="100%">Receptors, Neuropeptide</style></keyword><keyword><style  face="normal" font="default" size="100%">RNA, Messenger</style></keyword><keyword><style  face="normal" font="default" size="100%">Signal Transduction</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2006</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2006</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">84</style></volume><pages><style face="normal" font="default" size="100%">353-63</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">Orexin A, a recently discovered hypothalamic peptide, has been shown to have a stimulatory effect on release of gonadotropin-releasing hormone (GnRH) from rat hypothalamic explants in vitro. However, it is presently unclear whether in vivo this effect is mediated directly at the level of the GnRH neuron, or via multiple afferent neuronal connections. Therefore, in the present study, we investigated the direct action of orexin A on GnRH neurons using the immortalized GnRH-secreting GT1-7 hypothalamic cells. Orexin-1 receptor (OX1R) expression was detected in GT1-7 cells by RT-PCR and Western blot. Results showed that 0.1-1 nM orexin A, when administered in culture media for 4 h, can significantly stimulate GnRH mRNA expression in GT1-7 cells (p &lt; 0.05). Administration of 1 microM OX1R antagonist, SB-334867, completely blocked the observed orexin A responses in these cells, indicating that orexin A stimulation of GnRH neurons is specifically through OX1R. Moreover, 0.1 nM orexin A stimulated GnRH release after 30-45 min. To examine possible signal transduction pathways involved in mediating these effects, a MEK inhibitor (UO-126), PKC inhibitor (calphostin C), and PKA inhibitor (H-89), were used, with each blocking orexin A-induced GnRH transcription and release from immortalized cells. Collectively, our results show that orexin A is capable of directly stimulating GnRH transcription and neuropeptide release from these immortalized hypothalamic neurons, and that the effects of orexin A appear to be mediated via the OX1R, coupled with activation of the PKC-, MAPK- and PKA-signaling pathways. It is suggested that the stimulatory effect of orexin A on GnRH transcription and release may also occur directly at the level of GnRH neurons in vivo.</style></abstract><issue><style face="normal" font="default" size="100%">6</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/17192702?dopt=Abstract</style></custom1></record></records></xml>