Effects of Insufficient Sleep on Pituitary-Adrenocortical Response to CRH Stimulation in Healthy Men

Sleep. 2017 Jun 1;40(6):zsx064. doi: 10.1093/sleep/zsx064.


Study objectives: Severe sleep restriction results in elevated evening cortisol levels. We examined whether this relative hypercortisolism is associated with alterations in the pituitary-adrenocortical response to evening corticotropin-releasing hormone (CRH) stimulation.

Methods: Eleven subjects participated in 2 sessions (2 nights of 10 hours vs. 4 hours in bed) in randomized order. Sleep was polygraphically recorded. After the second night of each session, blood was sampled at 20-minute intervals from 09:00 to 24:00 for adrenocorticotropic hormone (ACTH) and cortisol measurements, and perceived stress was assessed hourly. Ovine CRH was injected at 18:00 (1 µg/kg body weight).

Results: Prior to CRH injection, baseline ACTH, but not cortisol, levels were elevated after sleep restriction. Relative to the well-rested condition, sleep restriction resulted in a 27% decrease in overall ACTH response to CRH (estimated by the incremental area under the curve from 18:00 to 24:00; p = .002) while the cortisol response was decreased by 21% (p = .083). Further, the magnitude of these decreases was correlated with the individual amount of sleep loss (ACTH: rSp = -0.65, p = .032; cortisol: rSp = -0.71, p = .015). The acute post-CRH increment of cortisol was reduced (p = .002) without changes in ACTH reactivity, suggesting decreased adrenal sensitivity. The rate of decline from peak post-injection levels was reduced for cortisol (p = .032), but not for ACTH. Scores of perceived stress were unaffected by CRH injection and were low and similar under both sleep conditions.

Conclusions: Sleep restriction is associated with a reduction of the overall ACTH and cortisol responses to evening CRH stimulation, and a reduced reactivity and slower recovery of the cortisol response.

Keywords: ACTH; CRH; HPA axis; cortisol; sleep; stress..

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Adrenocorticotropic Hormone / blood
  • Adult
  • Animals
  • Corticotropin-Releasing Hormone / pharmacology*
  • Cross-Over Studies
  • Female
  • Healthy Volunteers
  • Humans
  • Hydrocortisone / blood
  • Male
  • Pituitary-Adrenal System / drug effects*
  • Pituitary-Adrenal System / physiopathology
  • Random Allocation
  • Sheep
  • Sleep / drug effects
  • Sleep / physiology*
  • Sleep Deprivation / physiopathology*
  • Stress, Psychological / blood
  • Stress, Psychological / diagnosis
  • Young Adult


  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone
  • Hydrocortisone