Influences of Corticotropin-Releasing Hormone, Adrenocorticotropin, and Cortisol on Sleep in Normal Man*

Born, Jan; Späth‐Schwalbe, E.; Schwakenhofer, H.; Kern, W.; Fehm, Horst L.

doi:10.1210/jcem-68-5-904

Cited by 160 publications

(62 citation statements)

References 22 publications

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“…Finally, Vgontzas et al (2001) demonstrated that peripheral CRF infusion in healthy middle-aged men results in a greater decline in delta sleep than in healthy young men. Other studies of CRF infusion in young men have found either a decrease in delta sleep (Holsboer et al, 1988) or no effect on sleep (Born et al, 1989). Exogenous CRF does not cross the blood-brain barrier (Martins et al, 1996) but can Delta sleep response to metyrapone in PSTD TC Neylan et al affect periventricular structures, particularly the hypothalamus.…”

Section: Discussionmentioning

confidence: 98%

“…Theoretically, the decrease in delta sleep could be related to changes in pituitary ACTH or adrenal cortisol release. However, ACTH infusion has been shown to suppress REM but not slowwave sleep, which argues against the primary role of ACTH in decreasing delta (Born et al, 1989;Gillin et al, 1974a). Further, many studies show that cortisol infusion increases delta sleep (Bohlhalter et al, 1997;Born et al, 1991Born et al, , 1989Fehm et al, 1986;Hartog, 1964).…”

Section: Discussionmentioning

confidence: 99%

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Delta Sleep Response to Metyrapone in Post-Traumatic Stress Disorder

Neylan

Lenoci

Maglione

et al. 2003

Neuropsychopharmacol

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Metyrapone blocks cortisol synthesis, which results in the stimulation of hypothalamic cortiocotropin-releasing factor (CRF) and a reduction in delta sleep. We examined the effect of metyrapone administration on endocrine and sleep measures in male subjects with and without chronic PTSD. We hypothesized that metyrapone would result in a decrease in delta sleep and that the magnitude of this decrease would be correlated with the endocrine response. Finally, we utilized the delta sleep response to metyrapone as an indirect measure of hypothalamic CRF activity and hypothesized that PTSD subjects would have decreased delta sleep at baseline and a greater decrease in delta sleep induced by metyrapone. Three nights of polysomnography were obtained in 24 male subjects with combatrelated PTSD and 18 male combat-exposed normal controls. On day 3, metyrapone was administered during normal waking hours until habitual sleep onset preceding night 3. Endocrine responses to metyrapone were measured in plasma obtained the morning following sleep recordings, the day before and after administration. Repeated measures ANOVAs were conducted to compare the endocrine and sleep response to metyrapone in PTSD and controls. PTSD subjects had significantly less delta sleep as indexed by stages 3 and 4, and total delta integrated amplitude prior to metyrapone administration. There were no differences in premetyrapone cortisol or ACTH levels in PTSD vs controls. PTSD subjects had a significantly decreased ACTH response to metyrapone compared to controls. Metyrapone caused an increase in awakenings and a marked decrease in quantitative measures of delta sleep that was significantly greater in controls compared to PTSD. The decline in delta sleep was significantly associated with the magnitude of increase in both 11-deoxycortisol and ACTH. The results suggest that the delta sleep response to metyrapone is a measure of the brain response to increases in hypothalamic CRF. These data also suggest that the ACTH and sleep EEG response to hypothalamic CRF is decreased in PTSD.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Delta Sleep Response to Metyrapone in Post-Traumatic Stress Disorder

Neylan

Lenoci

Maglione

et al. 2003

Neuropsychopharmacol

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“…This may be related to either absolute cortisol levels or possibly to a reduction in the levels of CRH or ACTH. However, there is an optimum to be attained since high doses of exogenous glucocorticoids in normal individuals reduce REM sleep (35), and patients on higher doses of nocturnal glucocorticoid frequently report sleep disturbance.…”

Section: Sleep Disturbancesmentioning

confidence: 99%

“…One option is to wake at 0300 h to take immediate-release HC, a strategy that resulted in a significant improvement in 17 OH-progesterone, testosterone and individual (94). This is, however, not a practical solution for the majority of patients with adrenal insufficiency, and taking doses of longer acting glucocorticoids at night is associated with impaired sleep (35). Physiological hormone replacement, using sustained formulations of HC, should be the safest, most effective and practical solution.…”

Section: Circadian Glucocorticoid Therapymentioning

confidence: 99%

Inadequacies of glucocorticoid replacement and improvements by physiological circadian therapy

Debono

Ross²,

Newell‐Price

2009

European Journal of Endocrinology

114

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Patients with adrenal insufficiency need lifelong glucocorticoid replacement, but many suffer from poor quality of life, and overall there is increased mortality. Moreover, it appears that use of glucocorticoids at the higher end of the replacement dose range is associated with increased risk for cardiovascular and metabolic bone disease. These data highlight some of the inadequacies of current regimes.The cortisol production rate is estimated to be equivalent to 5.7-7.4 mg/m 2 per day, and a major difficulty for replacement regimes is the inability to match the distinct circadian rhythm of circulating cortisol levels, which are low at the time of sleep onset, rise between 0200 and 0400 h, peaking just after waking and then fall during the day. Another issue is that current dose equivalents of glucocorticoids used for replacement are based on anti-inflammatory potency, and few data exist as to doses needed for equivalent cardiovascular and bone effects. Weight-adjusted, thrice-daily dosing using hydrocortisone (HC) reduces glucocorticoid overexposure and represents the most refined regime for current oral therapy, but does not replicate the normal cortisol rhythm. Recently, proof-of-concept studies have shown that more physiological circadian glucocorticoid therapy using HC infusions and newly developed oral formulations of HC have the potential for better biochemical control in patients with adrenal insufficiency. Whether such physiological replacement will have an impact on the complications seen in patients with adrenal insufficiency will need to be analysed in future clinical trials.

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“…injections of CRH 7 and continuous i.v. infusion of ACTH 8 produced reductions of slow-wave sleep (SWS), correspondingly non-rapid eye movement (non-REM) sleep in rodents. Likewise, intracerebroventricular (i.c.v.)…”

Section: Introductionmentioning

confidence: 99%

Conditional corticotropin-releasing hormone overexpression in the mouse forebrain enhances rapid eye movement sleep

Kimura

Müller-Preuß

et al. 2009

Mol Psychiatry

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Impaired sleep and enhanced stress hormone secretion are the hallmarks of stress-related disorders, including major depression. The central neuropeptide, corticotropin-releasing hormone (CRH), is a key hormone that regulates humoral and behavioral adaptation to stress. Its prolonged hypersecretion is believed to play a key role in the development and course of depressive symptoms, and is associated with sleep impairment. To investigate the specific effects of central CRH overexpression on sleep, we used conditional mouse mutants that overexpress CRH in the entire central nervous system (CRH-COE-Nes) or only in the forebrain, including limbic structures (CRH-COE-Cam). Compared with wild-type or control mice during baseline, both homozygous CRH-COE-Nes and -Cam mice showed constantly increased rapid eye movement (REM) sleep, whereas slightly suppressed non-REM sleep was detected only in CRH-COE-Nes mice during the light period. In response to 6-h sleep deprivation, elevated levels of REM sleep also became evident in heterozygous CRH-COE-Nes and -Cam mice during recovery, which was reversed by treatment with a CRH receptor type 1 (CRHR1) antagonist in heterozygous and homozygous CRH-COE-Nes mice. The peripheral stress hormone levels were not elevated at baseline, and even after sleep deprivation they were indistinguishable across genotypes. As the stress axis was not altered, sleep changes, in particular enhanced REM sleep, occurring in these models are most likely induced by the forebrain CRH through the activation of CRHR1. CRH hypersecretion in the forebrain seems to drive REM sleep, supporting the notion that enhanced REM sleep may serve as biomarker for clinical conditions associated with enhanced CRH secretion.

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Influences of Corticotropin-Releasing Hormone, Adrenocorticotropin, and Cortisol on Sleep in Normal Man*

Cited by 160 publications

References 22 publications

Delta Sleep Response to Metyrapone in Post-Traumatic Stress Disorder

Delta Sleep Response to Metyrapone in Post-Traumatic Stress Disorder

Inadequacies of glucocorticoid replacement and improvements by physiological circadian therapy

Conditional corticotropin-releasing hormone overexpression in the mouse forebrain enhances rapid eye movement sleep

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