Orexin a stimulates hypothalamic-pituitary-adrenal (HPA) axis function, but not food intake, in the absence of full hypothalamic NPY-ergic activity

Endocrine. 2005 Mar;26(2):99-106. doi: 10.1385/ENDO:26:2:099.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenocorticotropic Hormone / blood
  • Animals
  • Body Weight / physiology
  • Corticosterone / blood
  • Eating / drug effects*
  • Eating / physiology
  • Female
  • Food Deprivation / physiology
  • Hypothalamo-Hypophyseal System / drug effects*
  • Hypothalamo-Hypophyseal System / physiology
  • Intracellular Signaling Peptides and Proteins / pharmacology*
  • Leptin / blood
  • Neuropeptide Y / genetics
  • Neuropeptide Y / physiology*
  • Neuropeptides / pharmacology*
  • Orexins
  • Pituitary-Adrenal System / drug effects*
  • Pituitary-Adrenal System / physiology
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sodium Glutamate / pharmacology
  • Statistics, Nonparametric

Substances

  • Intracellular Signaling Peptides and Proteins
  • Leptin
  • Neuropeptide Y
  • Neuropeptides
  • Orexins
  • RNA, Messenger
  • Adrenocorticotropic Hormone
  • Sodium Glutamate
  • Corticosterone