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

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: 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..

Figure 1

Schematic representation of the experimental protocol. Subjects participated in 2 laboratory sessions presented in randomized order: one involved 2 nights of 10 hours in bed (black bars) and the other involved 2 nights of 4 hours in bed (light grey bars). Sleep was polygraphically recorded during each night. After the second night of each experimental session, bedtime was at 24:00, an injection of ovine CRH (1 µg/kg body weight) was performed at 18:00 and blood samples were obtained at 20-minute intervals from 09:00 to bedtime while meals were replaced by constant glucose infusion at a rate of 5 g/kg/24 h. Measures of perceived stress were obtained at hourly intervals. TIB: time in bed; B: Breakfast; D: dinner; CRH: corticotropin-releasing hormone; q: every.

Figure 2

(a). ACTH and cortisol profiles pre- and post- CRH injection at 18:00 in the 10 hours in bed condition (left panels) and in the 4 hours in bed condition (right panels). The solid lines represent the median and the dotted lines represent the 25th and 75th percentiles. The time of CRH injection is indicated by the arrows. (b). Box and whisker plots of means of ACTH and cortisol pre-oCRH injection, that is, from 9:00 to 18:00. The line inside the box shows the median, the ends of the box are the 25th and 75th percentiles, the whiskers represent the largest and smallest observed values that are not outliers, and the dots represents outliers defined as 1.5 * interquartile range. p levels are from Wilcoxon test. ACTH: adrenocorticotropic hormone, CRH: corticotropin-releasing hormone.

Figure 3

(a). Relative ACTH and cortisol responses to CRH injection in the 10 hours in bed condition (left panel) and in the 4 hours in bed condition (right panel). The solid lines represent the median and the dotted lines represent the 25th and 75th percentiles. (b). Box and whisker plots of overall ACTH and cortisol responses to CRH injection (AUC above baseline 18:00 to 24:00). The line inside the box shows the median, the ends of the box are the 25th and 75th percentiles, the whiskers represent the largest and smallest observed values that are not outliers, and the dots represents outliers defined as 1.5 * interquartile range. p levels are from Wilcoxon test. ACTH: adrenocorticotropic hormone, CRH: corticotropin-releasing hormone, AUC: area under the curve.

Figure 4

Associations between the reduction in total sleep time (assessed by subtracting the total sleep time on the last 4 hours night to the total sleep time on the last 10 hours night) and the changes in pituitary–adrenocortical response to CRH injection (AUC above baseline 18:00 to 24:00). The reduction in total sleep time was inversely correlated to the changes in ACTH (a) and cortisol (b) overall response after CRH injection. ACTH: adrenocorticotropic hormone, CRH: corticotropin-releasing hormone.

Figure 5

Hourly scores on the five-point scale for “nervous” and on the 10-cm visual analog scales for “tense” and “calm” after 2 nights of 10 hours in bed (left panels) and after 2 nights of 4 hours in bed (right panels). The solid lines represent the median and the dotted lines represent the 25th and 75th percentiles. The arrows represent the time of CRH injection (18:00). There were no significant effects of time in bed duration on any of these three markers of self-perceived stress measures for both the pre- and post- CRH injection periods. CRH: corticotropin-releasing hormone.