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Endocrinology ; 144(7): 3225-36, 2003 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-12810579

RESUMEN

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.


Asunto(s)
Proteínas Portadoras/farmacología , Estradiol/análogos & derivados , Péptidos y Proteínas de Señalización Intracelular , Hormona Luteinizante/metabolismo , Neuropéptidos/farmacología , Área Preóptica/efectos de los fármacos , Área Preóptica/metabolismo , Urea/análogos & derivados , Animales , Benzoxazoles/farmacología , Proteínas Portadoras/metabolismo , Células Cultivadas , Estradiol/farmacología , Femenino , Hormona Liberadora de Gonadotropina/metabolismo , Inmunohistoquímica , Microinyecciones , Naftiridinas , Neuropéptidos/metabolismo , Receptores de Orexina , Orexinas , Ovariectomía , Área Preóptica/citología , Progesterona/farmacología , Ratas , Ratas Wistar , Receptores Acoplados a Proteínas G , Receptores de Neuropéptido/antagonistas & inhibidores , Urea/farmacología
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