Effects of orexins on the hypothalamic-pituitary-adrenal system

J Neuroendocrinol. 2000 Dec;12(12):1174-8. doi: 10.1046/j.1365-2826.2000.00572.x.


The effects of the recently identified neuropeptides orexin-A and orexin-B on the hypothalamic-pituitary-adrenal (HPA) system were investigated. An in vivo system was used to assess the central effects of both orexin-A and orexin-B. Different doses of the orexins (2.8-560 pmol) were administered intracerebroventricularly (i.c.v.) to adult male rats, and plasma corticosterone was used as an index of the degree of the activation of the HPA system. Both peptides exhibited a clear dose-response action, although orexin-B proved to be less effective than orexin-A. Pretreatment with the corticotropin-releasing hormone (CRH) antagonist alpha-helical CRH9-41 completely prevented the action of the orexins. Orexin-A, orexin-B or adrenocorticotropic hormone (ACTH) was further administered intraperitoneally (i.p.). While ACTH evoked a significant adrenal response, the orexins did not influence the basal secretion. Adrenal slices, oxygenized and perifused with Krebs' solution, were also treated with orexin-A, orexin-B or ACTH. Both orexins failed to modify the release of corticosterone, but ACTH induced a marked adrenal response. This study suggests that these appetite-regulating peptides might activate the HPA system at a central level but neither orexin-A nor orexin-B appears to modulate directly the adrenal corticosterone release.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Glands / drug effects
  • Adrenal Glands / metabolism
  • Adrenocorticotropic Hormone / metabolism
  • Adrenocorticotropic Hormone / pharmacology
  • Animals
  • Carrier Proteins / pharmacology*
  • Corticosterone / metabolism
  • Corticotropin-Releasing Hormone / pharmacology
  • Hormone Antagonists / pharmacology
  • Hypothalamo-Hypophyseal System / drug effects*
  • Hypothalamo-Hypophyseal System / metabolism
  • Hypothalamo-Hypophyseal System / physiology
  • In Vitro Techniques
  • Injections, Intraperitoneal
  • Injections, Intraventricular
  • Intracellular Signaling Peptides and Proteins*
  • Male
  • Neuropeptides / pharmacology*
  • Orexins
  • Peptide Fragments / pharmacology
  • Pituitary-Adrenal System / drug effects*
  • Pituitary-Adrenal System / metabolism
  • Pituitary-Adrenal System / physiology
  • Rats
  • Rats, Wistar


  • Carrier Proteins
  • Hormone Antagonists
  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Orexins
  • Peptide Fragments
  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone
  • corticotropin releasing hormone (9-41)
  • Corticosterone