In vivo action of a new octadecaneuropeptide (ODN) antagonist on gonadotropin-releasing hormone gene expression in the male rat brain.
It has been reported that several of the effects induced by octadecaneuropeptide (ODN) could be mediated by an activation of a metabotropic receptor. In order to investigate the role and mechanism of action of ODN in gonadotropin-releasing hormone (GnRH) neuron regulation, we studied the effects of the acute i.c.v. administration of ODN and of a new ODN antagonist to metabotropic receptor, cyclo(1-8)[Dleu(5)]OP, on GnRH mRNA expression as evaluated by in situ hybridization in castrated male rats. The administration of ODN produced a decrease in the hybridization signal while the administration of cyclo(1-8)[Dleu(5)]OP alone produced an 18% increase. When administrated concomitantly with ODN, the antagonist both inhibited the depressing effect of ODN and induced a 22% increase over the values detected in ODN-treated rats. The data suggest that the effect of ODN on GnRH mRNA expression might be mediated by interaction with metabotropic receptors.
Compère
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European Institute for Peptide Research (IFRMP 23), Laboratory of Cellular and Molecular Neuroendocrinology, INSERM U413, UA CNRS, University of Rouen, Mont-Saint-Aignan, France.
Li
S
S
Leprince
J
J
Tonon
M C
MC
Vaudry
H
H
Pelletier
G
G
D000818:Animals; D002369:Castration / Q000379:methods; D026261:Diazepam Binding Inhibitor; D004347:Drug Interactions; D015870:Gene Expression / Q000187:drug effects*; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D009479:Neuropeptides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010446:Peptide Fragments; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D026261:Diazepam Binding Inhibitor; D009479:Neuropeptides; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D012333:RNA, Messenger; C487836:cyclo(Arg-Pro-Gly-Leu-Leu-Asp-Leu-Lys); C067529:diazepam binding inhibitor (33-50); D007987:Gonadotropin-Releasing Hormone