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

• Published in: Sleep (New York, N.Y.) Vol. 40; no. 6
• Main Authors: Guyon, Aurore, Morselli, Lisa L., Balbo, Marcella L., Tasali, Esra, Leproult, Rachel, L’Hermite-Balériaux, Mireille, Van Cauter, Eve, Spiegel, Karine
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.06.2017
• Subjects: Adolescent; Adrenocorticotropic Hormone - blood; Adult; Animals; Corticotropin-Releasing Hormone - pharmacology; Cross-Over Studies; Female; Healthy Volunteers; Humans; Hydrocortisone - blood; Male; Original; 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; sleep; ACTH; CRH; cortisol; stress; HPA axis
• ISSN: 0161-8105; 1550-9109; 1550-9109
• DOI: 10.1093/sleep/zsx064

Abstract 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: r Sp = −0.65, p = .032; cortisol: r Sp = −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.