Orexin a stimulates hypothalamic-pituitary-adrenal (HPA) axis function, but not food intake, in the absence of full hypothalamic NPY-ergic activity.
Neonatal monosodium L-glutamate (MSG) treatment destroys hypothalamic arcuate nucleus neuronal bodies, thus inducing several metabolic abnormalities. As a result, rats develop a phenotype characterized by hyperleptinemia and by impaired NPY but normal preproorexin hypothalamic mRNAs expression. Thus, our study was designed to explore whether hypothalamic effects of orexin A on food intake and glucocorticoid production develop in the absence of full hypothalamic NPY-ergic activity. For this purpose we evaluated, in control and MSG-treated rats, the consequences of intracerebroventricular (icv) orexin A administration on food intake and changes in circulating levels of ACTH and glucocorticoid. Our results indicate that orexin A icv treatment stimulated hypothalamic-pituitary-adrenal (HPA) axis activity in both MSG-damaged and normal animals, with this response even more pronounced in neurotoxin-damaged rats. Conversely, food intake was only enhanced by icv orexin A injection in normal rats. Our study further supports that acute hypothalamic effects of orexin A on food intake and glucocorticoid production are due to independent neuronal systems. While intact arcuate nucleus activity is needed for the orexinergic effect induced by icv orexin A administration, conversely, orexin A-stimulated HPA axis function takes place even in the absence of full NPY-ergic activity.
Moreno
Griselda
G
Neuroendocrine Unit, Multidisciplinary Institute on Cell Biology (CONICET-CICPBA), 1900 La Plata, Argentina.
Perelló
Mario
M
Gaillard
Rolf C
RC
Spinedi
Eduardo
E
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001835:Body Weight / Q000502:physiology; D003345:Corticosterone / Q000097:blood; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005508:Food Deprivation / Q000502:physiology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology*; D020738:Leptin / Q000097:blood; D009478:Neuropeptide Y / Q000235:genetics / Q000502:physiology*; D009479:Neuropeptides / Q000494:pharmacology*; D000068797:Orexins; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012970:Sodium Glutamate / Q000494:pharmacology; D018709:Statistics, Nonparametric
D047908:Intracellular Signaling Peptides and Proteins; D020738:Leptin; D009478:Neuropeptide Y; D009479:Neuropeptides; D000068797:Orexins; D012333:RNA, Messenger; D000324:Adrenocorticotropic Hormone; D012970:Sodium Glutamate; D003345:Corticosterone