title: Central orexin A has site-specific effects on luteinizing hormone release in female rats.
abstract: Orexin A stimulates GnRH release from hypothalamic explants in vitro. The sites of action of orexin A in the regulation of LH release have been investigated in vivo in ovariectomized rats that were given vehicle or estradiol benzoate (EB), with or without an injection of progesterone 48 h later. Orexin A was administered intrahypothalamically under Saffan anesthesia, 50 h after the EB or vehicle; its effects on plasma LH levels were monitored in sequential blood samples. Orexin A (1.0 microg/side) injected into the rostral preoptic area (rPOA) at the level of the organum vasculosum of the lamina terminalis had a stimulatory effect on LH release in EB-treated ovariectomized rats. When orexin A was injected into the medial POA (mPOA) or the arcuate/median eminence, it had an inhibitory effect on the LH surge that occurs in ovariectomized rats primed with EB plus progesterone. Orexin A injected into the mPOA also reduced LH levels in ovariectomized rats untreated with ovarian steroids. Both the stimulatory and inhibitory effects of orexin A were antagonized by SB334867A, a selective orexin 1 receptor antagonist. Furthermore, when given alone into the rPOA, this antagonist attenuated the LH surge induced by EB plus progesterone. Thus, orexin appears to have a dual effect on LH release, being stimulatory in the rPOA and inhibitory in the mPOA or arcuate/median eminence. Both effects may be mediated, at least in part, by the orexin 1 receptor. Double label immunohistochemistry revealed close appositions between orexin A immunoreactive varicosities and a small proportion of GnRH cell bodies in the rPOA. It is suggested that the stimulatory effect of orexin A on LH release may involve direct actions on GnRH neurons.
authors.affiliation: Department of Obstetrics, St. George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, United Kingdom.
authors.forename: C J
authors.initials: CJ
authors.lastname: Small
authors.forename: M-L
authors.initials: ML
authors.lastname: Goubillon
authors.forename: J F
authors.initials: JF
authors.lastname: Murray
authors.forename: A
authors.initials: A
authors.lastname: Siddiqui
authors.forename: S E
authors.initials: SE
authors.lastname: Grimshaw
authors.forename: H
authors.initials: H
authors.lastname: Young
authors.forename: V
authors.initials: V
authors.lastname: Sivanesan
authors.forename: T
authors.initials: T
authors.lastname: Kalamatianos
authors.forename: A R
authors.initials: AR
authors.lastname: Kennedy
authors.forename: C W
authors.initials: CW
authors.lastname: Coen
authors.forename: S R
authors.initials: SR
authors.lastname: Bloom
authors.forename: C A
authors.initials: CA
authors.lastname: Wilson
mesh_terms: D000818:Animals; D001583:Benzoxazoles / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D007986:Luteinizing Hormone / Q000378:metabolism*; D008845:Microinjections; D009287:Naphthyridines; D009479:Neuropeptides / Q000378:metabolism / Q000494:pharmacology*; D064446:Orexin Receptors; D000068797:Orexins; D010052:Ovariectomy; D011301:Preoptic Area / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D001583:Benzoxazoles; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009287:Naphthyridines; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; C074283:estradiol 3-benzoate; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol; D014508:Urea; D007986:Luteinizing Hormone