Sleep and the hypothalamo-pituitary-adrenocortical system

Sleep Med Rev. 2002 Apr;6(2):125-38. doi: 10.1053/smrv.2001.0159.


The intention of this review is to summarize the current knowledge on the bidirectional interaction between sleep EEG and the secretion of corticotropin (ACTH) and cortisol. The administration of various hypothalamic-pituitary- adrenocortical (HPA) hormones and their antagonists exerts specific sleep-EEG changes in several species including humans. It is well documented that corticotropin releasing hormone (CRH) impairs sleep and enhances vigilance. In addition, it may promote REM sleep. Changes in the growth hormone-releasing hormone (GHRH):CRH ratio in favour of CRH appear to contribute to shallow sleep, elevated cortisol levels and blunted GH in depression and ageing. On the other hand, in women GHRH appears to exert CRH-like effects on sleep. Acute cortisol administration increases slow-wave sleep (SWS) and GH, probably due to feedback inhibition of CRH, and inhibits REM sleep. With the mixed glucocorticoid and progesterone receptor antagonist mifepriston sleep is disrupted. Subchronic administration of the glucocorticoid agonist methylprednisolone desinhibited REM sleep. A synergism of elevated CRH and cortisol activity may contribute to REM disinhibition during depression. Also ACTH and vasopressin modulate sleep specifically but their physiological role remains unclear. For example acute icv vasopressin enhances wakefulness in rats, whereas its long-term administration increases SWS in the elderly. In various studies the interaction of sleep EEG and HPA hormones has been investigated at the baseline, after manipulation of sleep-wake behaviour and after environmental changes. Most studies agree that the circadian pattern of cortisol is relatively independent from sleep and environmental influences. Some data suggest a major effect of light on cortisol secretion. Sleeping is widely associated with blunting and awakenings are linked with increases of HPA hormones.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adrenocorticotropic Hormone / metabolism
  • Corticotropin-Releasing Hormone / metabolism
  • Electroencephalography
  • Growth Hormone-Releasing Hormone / metabolism
  • Humans
  • Hydrocortisone / metabolism
  • Hypothalamo-Hypophyseal System / metabolism*
  • Pituitary-Adrenal System / metabolism*
  • Sleep Disorders, Circadian Rhythm / metabolism
  • Sleep, REM / physiology*


  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone
  • Growth Hormone-Releasing Hormone
  • Hydrocortisone