title: The orexigenic effect of orexin-A revisited: dependence of an intact growth hormone axis.
abstract: Fifteen years ago orexins were identified as central regulators of energy homeostasis. Since then, that concept has evolved considerably and orexins are currently considered, besides orexigenic neuropeptides, key modulators of sleep-wake cycle and neuroendocrine function. Little is known, however, about the effect of the neuroendocrine milieu on orexins' effects on energy balance. We therefore investigated whether hypothalamic-pituitary axes have a role in the central orexigenic action of orexin A (OX-A) by centrally injecting hypophysectomized, adrenalectomized, gonadectomized (male and female), hypothyroid, and GH-deficient dwarf rats with OX-A. Our data showed that the orexigenic effect of OX-A is fully maintained in adrenalectomized and gonadectomized (females and males) rats, slightly reduced in hypothyroid rats, and totally abolished in hypophysectomized and dwarf rats when compared with their respective vehicle-treated controls. Of note, loss of the OX-A effect on feeding was associated with a blunted OX-A-induced increase in the expression of either neuropeptide Y or its putative regulator, the transcription factor cAMP response-element binding protein, as well as its phosphorylated form, in the arcuate nucleus of the hypothalamus of hypophysectomized and dwarf rats. Overall, this evidence suggests that the orexigenic action of OX-A depends on an intact GH axis and that this neuroendocrine feedback loop may be of interest in the understanding of orexins action on energy balance and GH deficiency.
authors.affiliation: Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain and CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Spain. m.lopez@usc.es.
authors.forename: Mayte
authors.initials: M
authors.lastname: Álvarez-Crespo
authors.forename: Noelia
authors.initials: N
authors.lastname: Martínez-Sánchez
authors.forename: Francisco
authors.initials: F
authors.lastname: Ruíz-Pino
authors.forename: Montserrat
authors.initials: M
authors.lastname: Garcia-Lavandeira
authors.forename: Clara V
authors.initials: CV
authors.lastname: Alvarez
authors.forename: Manuel
authors.initials: M
authors.lastname: Tena-Sempere
authors.forename: Rubén
authors.initials: R
authors.lastname: Nogueiras
authors.forename: Carlos
authors.initials: C
authors.lastname: Diéguez
authors.forename: Miguel
authors.initials: M
authors.lastname: López
mesh_terms: D000315:Adrenalectomy / Q000009:adverse effects; D000818:Animals; D001069:Appetite Regulation; D002369:Castration / Q000009:adverse effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis / Q000378:metabolism; D004393:Dwarfism, Pituitary / Q000378:metabolism / Q000503:physiopathology; D005247:Feeding Behavior; D005260:Female; D013006:Growth Hormone / Q000378:metabolism*; D007016:Hypophysectomy / Q000009:adverse effects; D007031:Hypothalamus / Q000378:metabolism; D007037:Hypothyroidism / Q000378:metabolism / Q000503:physiopathology; D007276:Injections, Intraventricular; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism*; D009478:Neuropeptide Y / Q000096:biosynthesis / Q000378:metabolism; D009479:Neuropeptides / Q000008:administration & dosage / Q000378:metabolism*; D000068797:Orexins; D010902:Pituitary Gland / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D011986:Receptors, Somatotropin / Q000378:metabolism*
chemical_list: C508137:Creb1 protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D047908:Intracellular Signaling Peptides and Proteins; D009478:Neuropeptide Y; D009479:Neuropeptides; D000068797:Orexins; D011986:Receptors, Somatotropin; D013006:Growth Hormone