Chronic cold in adrenalectomized, corticosterone (B)-treated rats: facilitated corticotropin responses to acute restraint emerge as B increases

Endocrinology. 1997 Aug;138(8):3249-58. doi: 10.1210/endo.138.8.5291.


Small elevations in corticosterone (B) administered exogenously exert potent inhibitory effects on both basal and stress-induced ACTH secretion. However, under conditions of chronic stress with chronic elevations in B, the hypothalamo-pituitary-adrenal system appears to balance the negative feedback signal of B with central neural facilitation so that the system remains fully responsive to acute stressors. In these studies, we tested whether: 1) circulating B concentrations affect responses to acute restraint in rats exposed to 5 days at 5-7 C (cold), compared with room temperature (control); and 2) facilitated ACTH secretion can be explained by increased CRF or vasopressin messenger RNA (mRNA) levels in the hypothalamic parvocellular paraventricular nuclei (PVN). Rats were adrenalectomized and supplied with B in doses that fixed plasma B at constant levels between approximately 2 and 20 microg/dl; rats were placed in cold or remained as controls. Increasing concentrations of fixed B decreased basal ACTH similarly in both groups. By contrast, as B levels increased, ACTH responses to restraint also increased in cold vs. control rats. Semiquantitative analysis of CRF mRNA by in situ hybridization revealed decreases of similar magnitude in both groups with increasing fixed B. Vasopressin mRNA levels also decreased with increasing fixed B in both groups, but with slightly less sensitivity to inhibition by B in cold exposed rats. Taken together, the decreases in mRNA for these major ACTH neuropeptide secretogogues in the parvocellular PVN are unlikely to explain facilitated ACTH responses in chronically stressed rats. We conclude that a brain site is stimulated by B that is proximal to the PVN; feedforward, positive effects of B are thus implicated in mediation of prior stress-induced facilitation of acute hypothalamo-pituitary-adrenal responses to stress.

MeSH terms

  • Adrenalectomy*
  • Adrenocorticotropic Hormone / analysis
  • Adrenocorticotropic Hormone / blood*
  • Animals
  • Circadian Rhythm
  • Cold Temperature*
  • Corticosterone / administration & dosage
  • Corticosterone / pharmacology*
  • Corticotropin-Releasing Hormone / analysis
  • Corticotropin-Releasing Hormone / biosynthesis
  • Corticotropin-Releasing Hormone / genetics
  • Dose-Response Relationship, Drug
  • Hypothalamo-Hypophyseal System / physiology
  • Hypothalamus / chemistry
  • In Situ Hybridization
  • Male
  • Paraventricular Hypothalamic Nucleus / chemistry
  • Pituitary Gland / chemistry
  • Pituitary-Adrenal System / physiology
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Restraint, Physical*
  • Stress, Physiological / etiology
  • Stress, Physiological / metabolism*
  • Thymus Gland / physiology
  • Time Factors
  • Vasopressins / analysis
  • Vasopressins / biosynthesis
  • Vasopressins / genetics


  • RNA, Messenger
  • Vasopressins
  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone
  • Corticosterone