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This version published online on April 17, 2003
Endocrinology, doi:10.1210/en.2002-0041
A more recent version of this article appeared on July 1, 2003
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Submitted on November 14, 2002
Accepted on April 3, 2003

Central orexin A has site-specific effects on luteinizing hormone release in female rats

C J Small1, M-L Goubillon1, J F Murray1, A Siddiqui1, S E Grimshaw1, H Young1, V Sivanesan1, T Kalamatianos1, A R Kennedy1, C W Coen1, S R Bloom1, and C A Wilson1*

1 Departments of Obstetrics & Gynaecology/Physiology, St George's Hospital Medical School, London, SW17 0RE.; *Department of Metabolic Medicine, Imperial College School of Medicine, Hammersmith Hospital, London, W12 0NN; Centre for Neuroscience Research, King's College London, Guy's Campus, London, SE1 1UL.

* To whom correspondence should be addressed. E-mail: cwilson{at}sghms.ac.uk.

OrexinA stimulates GnRH release from hypothalamic explants in vitro. The sites of action of orexinA in the regulation of LH release have been investigated in vivo in ovariectomised rats which were given vehicle or estradiol benzoate (OB), with or without an injection of progesterone (P) 48 h later. OrexinA was administered intrahypothalamically under Saffan anesthesia, 50 h after the OB or vehicle; its effects on plasma LH levels were monitored in sequential blood samples. OrexinA (1.0 µg/side) injected into the rostral preoptic area (rPOA) at the level of the OVLT had a stimulatory effect on LH release in OB-treated ovariectomised rats. When orexinA was injected into the medial POA (mPOA) or the arcuate/median eminence (ARC/ME) it had an inhibitory effect on the LH surge that occurs in ovariectomised rats primed with OB+P. OrexinA injected into the mPOA also reduced LH levels in ovariectomised rats untreated with ovarian steroids. Both the stimulatory and inhibitory effects of orexinA were antagonised by SB334867A, a selective orexin1 receptor antagonist. Furthermore, when given alone into the rPOA, this antagonist attenuated the LH surge induced by OB+P. Thus orexin appears to have a dual effect on LH release being stimulatory in the rPOA and inhibitory in the mPOA or ARC/ME. Both effects may be mediated, at least in part, by the orexin1 receptor. Double label immunohistochemistry revealed close appositions between orexinA immunoreactive varicosities and a small proportion of GnRH cell bodies in the rPOA. It is suggested that the stimulatory effect of orexinA on LH release may involve direct actions on GnRH neurons.
Key words: Orexin • luteinizing hormone • preoptic area • GnRH • SB • 334867-A • hypothalamic explants • double label immunohistochemistry • confocal microscopy




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