Central orexin-A activates hypothalamic-pituitary-adrenal axis and stimulates hypothalamic corticotropin releasing factor and arginine vasopressin neurones in conscious rats

J Neuroendocrinol. 2001 May;13(5):421-4. doi: 10.1046/j.1365-2826.2001.00655.x.

Abstract

The effects of centrally injected orexin-A on plasma adrenocorticotropin (ACTH) and corticosterone levels and corticotropin releasing factor (CRF) and arginine vasopressin (AVP) mRNA in the parvocellular cells of the paraventricular nucleus (PVN) of the rat were investigated. In animals implanted previously with a lateral brain ventricle and femoral artery cannula, a single i.c.v. injection of orexin-A (10 microg/rat) resulted in a rapid, significant increase in plasma ACTH and corticosterone concentrations. Plasma ACTH reached a peak (12.5-fold greater than basal levels) at 30 min, which was maintained over 120 min before declining towards control levels by 240 min. Plasma corticosterone concentrations reached a peak (6.7-fold greater than basal levels) at 30 min. Orexin-A at a higher dose (30 microg/rat) also produced a rapid increase in plasma ACTH and corticosterone concentrations. The area under the curve for plasma levels of ACTH was similar for both doses of orexin-A. In a second study, orexin-A (10 microg/rat) was injected i.c.v. and brains and pituitaries were rapidly removed after 240 min. In situ hybridization histochemistry revealed that CRF and AVP mRNA levels were significantly increased in the parvocellular cells of the PVN. Pro-opiomelanocortin mRNA levels in the pituitary gland were not significantly elevated in response to orexin-A. These results suggest that orexin-A is able to act centrally to activate the hypothalamic-pituitary-adrenal axis involving stimulation of both CRF and AVP expression.

MeSH terms

  • Adrenocorticotropic Hormone / blood
  • Animals
  • Arginine Vasopressin / genetics
  • Arginine Vasopressin / metabolism*
  • Carrier Proteins / pharmacology*
  • Consciousness
  • Corticosterone / blood
  • Corticotropin-Releasing Hormone / genetics
  • Corticotropin-Releasing Hormone / metabolism*
  • Gene Expression / drug effects
  • Hypothalamo-Hypophyseal System / cytology
  • Hypothalamo-Hypophyseal System / drug effects*
  • Hypothalamo-Hypophyseal System / metabolism
  • In Situ Hybridization
  • Injections, Intraventricular
  • Intracellular Signaling Peptides and Proteins*
  • Male
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neuropeptides / pharmacology*
  • Orexins
  • Pituitary-Adrenal System / cytology
  • Pituitary-Adrenal System / drug effects*
  • Pituitary-Adrenal System / metabolism
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Orexins
  • RNA, Messenger
  • Arginine Vasopressin
  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone
  • Corticosterone