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Neurochemical regulation of sleep
Abstract
This review summarizes recent developments in the field of sleep regulation, particularly in the role of hormones, and of synthetic GABA(A) receptor agonists. Certain hormones play a specific role in sleep regulation. A reciprocal interaction of the neuropeptides growth hormone (GH)-releasing hormone (GHRH) and corticotropin-releasing hormone (CRH) plays a key role in sleep regulation. At least in males GHRH is a common stimulus of non-rapid-eye-movement sleep (NREMS) and GH and inhibits the hypothalamo-pituitary adrenocortical (HPA) hormones, whereas CRH exerts opposite effects. Furthermore CRH may enhance rapid-eye-movement sleep (REMS). Changes in the GHRH:CRH ratio in favor of CRH appear to contribute to sleep EEG and endocrine changes during depression and normal ageing. In women, however, CRH-like effects of GHRH were found. Besides CRH somatostatin impairs sleep, whereas ghrelin, galanin and neuropeptide Y promote sleep. Vasoactive intestinal polypeptide appears to be involved in the temporal organization of human sleep. Beside of peptides, steroids participate in sleep regulation. Cortisol appears to promote REMS. Various neuroactive steroids exert specific effects on sleep. The beneficial effect of estrogen replacement therapy in menopausal women suggests a role of estrogen in sleep regulation. The GABA(A) receptor or GABAergic neurons are involved in the action of many of these hormones. Recently synthetic GABA(A) agonists, particularly gaboxadol and the GABA reuptake inhibitor tiagabine were shown to differ distinctly in their action from allosteric modulators of the GABA(A) receptor like benzodiazepines as they promote slow-wave sleep, decrease wakefulness and do not affect REMS.
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“Pregnancy causes significant changes in the neuroendocrine system, including gonadal steroids (estrogen and progesterone), pituitary hormones (gonadatrophins, prolactin, and growth hormone), melatonin, and cortisol [52,53].”
From Non-Pharmacological Treatment of Insomnia (2012) · cites this paper as [52]
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Hypothalamic growth hormone-releasing hormone mRNA varies across the day in rats
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On the Gender Differences in Sleep-Endocrine Regulation in Young Normal Humans
Antonijevic, I. A., Murck, H., Frieboes, R.-M., Holsboer, F., & Steiger, A. (1999) · Neuroendocrinology · doi:10.1159/000054487 · Cited by 63
Antonijevic, I., & Steiger, A. (2003) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(02)00085-9 · Cited by 61
The GABAA agonist gaboxadol improves the quality of post-nap sleep
Mathias, S., Steiger, A., & Lancel, M. (2001) · Psychopharmacology · doi:10.1007/s002130100819 · Cited by 61
Effect of prolactin on the sleep-wake cycle in the rat
Roky, R., Valatx, J. L., & Jouvet, M. (1993) · Neuroscience Letters · doi:10.1016/0304-3940(93)90453-r · Cited by 60
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Acute Cortisol Administration Promotes Sleep Intensity in Man
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Held, K., Antonijevic, I. A., Murck, H., Kuenzel, H., & Steiger, A. (2005) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2005.05.015 · Cited by 58
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Dose-Response Effects of Tiagabine on the Sleep of Older Adults
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Pregabalin Enhances Nonrapid Eye Movement Sleep
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Hypothalamic injection of prolactin or its antibody alters the rat sleep-wake cycle
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Corticotropin-releasing factor (CRF) increases paradoxical sleep (PS) rebound in PS-deprived rats
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Age-Dependent Suppression of Nocturnal Growth Hormone Levels during Sleep Deprivation
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Effects of chronic icv infusion of vasopressin on sleep-waking cycle of rats
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On the role of menopause for sleep-endocrine alterations associated with major depression
Antonijevic, I. A., Murck, H., Frieboes, R.-M., Uhr, M., & Steiger, A. (2003) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(02)00031-8 · Cited by 47
Sleep of transgenic mice producing excess rat growth hormone
Hajdu, I., Obál, F., Fang, J., Krueger, J. M., & Rollo, C. D. (2002) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00485.2001 · Cited by 46
Kindling Stimuli Delivered at Different Times in the Sleep-Wake Cycle
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Beneficial Treatment of Age-Related Sleep Disturbances With Prolonged Intranasal Vasopressin
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Modelling and exploring human sleep with event history analysis
Yassouridis, A., Steiger, A., Klinger, A., & Fahrmeir, L. (1999) · Journal of Sleep Research · doi:10.1046/j.1365-2869.1999.00133.x · Cited by 43
REM sleep deprivation induces galanin gene expression in the rat brain
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Effects of ACTH on the Sleep of Normal Subjects and Patients with Addison’s Disease
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Sleep in rats rendered chronically hyperprolactinemic with anterior pituitary grafts
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Antiserum to Growth Hormone Decreases Sleep in the Rat
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Ziegenbein, M., Held, K., Kuenzel, H., Murck, H., Antonijevic, I. A., & Steiger, A. (2003) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300298 · Cited by 40
VIP decelerates non-REM-REM cycles and modulates hormone secretion during sleep in men
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Antiserum to prolactin decreases rapid eye movement sleep (REM sleep) in the male rat
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Electroencephalographic sleep studies in depressed patients during long-term recovery
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GABA pharmacology—what prospects for the future?
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Frieboes, R.-M., Antonijevic, I. A., Held, K., Murck, H., Pollmächer, T., Uhr, M., & Steiger, A. (2003) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(03)00152-5 · Cited by 36
Galanin has REM-sleep deprivation-like effects on the sleep eeg in healthy young men
Murck, H., Antonijevic, I. A., Frieboes, R.-M., Maier, P., Schier, T., & Steiger, A. (1999) · Journal of Psychiatric Research · doi:10.1016/s0022-3956(98)00059-4 · Cited by 36
Decrease in Delta Sleep in Growth Hormone Deficiency Assessed by a New Power Spectrum Analysis
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Sleep endocrine effects of antigluco- and antimineralocorticoids in healthy males
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GarcIa-Borreguero, D. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.85.11.4201 · Cited by 35
Schneider, H. J., Oertel, H., Murck, H., Pollmächer, T., Stalla, G. K., & Steiger, A. (2004) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2004.05.004 · Cited by 34
Entrainment of Nocturnal Pituitary-Adrenocortical Activity to Sleep Processes in Man — A Hypothesis
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Sleep deprivation increases rat hypothalamic growth hormone-releasing hormone mRNA
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Steiger, A., Rupprecht, R., Spengler, D., Guldner, J., Hemmeter, U., Rothe, B., Damm, K., & Holsboer, F. (1993) · Journal of Psychiatric Research · doi:10.1016/0022-3956(93)90038-4 · Cited by 32
Antiglucocorticoid treatment disrupts endocrine cycle and nocturnal sleep pattern
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Sleep-endocrine effects of mifepristone and megestrol acetate in healthy men
Wiedemann, K., Lauer, C. J., Hirschmann, M., Knaudt, K., & Holsboer, F. (1998) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1998.274.1.e139 · Cited by 32
Effect size of efficacy measures comparing divalproex, lithium and placebo in acute mania
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Muscimol and Midazolam Do Not Potentiate Each Other's Effects on Sleep EEG in the Rat
Lancel, M., Faulhaber, J., Schiffelholz, T., Mathias, S., & Deisz, R. A. (1997) · Journal of Neurophysiology · doi:10.1152/jn.1997.77.3.1624 · Cited by 28
Effects of hCRH on sleep and body temperature rhythms
Tsuchiyama, Y., Uchimura, N., Sakamoto, T., Maeda, H., & Kotorii, T. (1995) · Psychiatry and Clinical Neurosciences · doi:10.1111/j.1440-1819.1995.tb01906.x · Cited by 28
The promnesic neurosteroid pregnenolone sulfate increases paradoxical sleep in rats
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Hemmeter, U., Rothe, B., Guldner, J., Holsboer, F., & Steiger, A. (1998) · Neuropsychobiology · doi:10.1159/000026513 · Cited by 25
The effect of SRIF on the EEG sleep of normal men
Kupfer, D. J., Jarrett, D. B., & Ehlers, C. L. (1992) · Psychoneuroendocrinology · doi:10.1016/0306-4530(92)90074-h · Cited by 25
Sleep Endocrine Effects of the 11-β-Hydroxysteroiddehydrogenase Inhibitor Metyrapone
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Elevated Plasma Ghrelin Levels in Night-Eating Syndrome
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Schiffelholz, T., Holsboer, F., & Lancel, M. (2000) · Physiology & Behavior · doi:10.1016/s0031-9384(00)00218-3 · Cited by 23
Aging does not affect the sleep endocrine response to total sleep deprivation in humans
Murck, H., Antonijevic, I. A., Schier, T., Frieboes, R.-M., Barthelmes, J., & Steiger, A. (1999) · Neurobiology of Aging · doi:10.1016/s0197-4580(99)00048-2 · Cited by 23
Lancel, M., & Langebartels, A. (2000) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)39335-8 · Cited by 23
Hyporesponsiveness of the Pituitary to CRH during Slow Wave Sleep Is Not Mimicked by Systemic GHRH
Antonijevic, I. A., Murck, H., Frieboes, R.-M., Holsboer, F., & Steiger, A. (1999) · Neuroendocrinology · doi:10.1159/000054406 · Cited by 22
Sleep-associated variations in plasma renin activity and blood pressure in the rat
Obál, F., Beranek, L., & BRANDENBERGER, G. (1994) · Neuroscience Letters · doi:10.1016/0304-3940(94)90940-7 · Cited by 20
Seifritz, E., Müller, M. J., Trachsel, L., Lauer, C. J., Hemmeter, U., Hatzinger, M., Moore, P., & Holsboer‐Trachsler, E. (1996) · Biological Psychiatry · doi:10.1016/0006-3223(95)00319-3 · Cited by 19
Minireview: Gender-specific sleep regulation*
Kimura, M. (2005) · Sleep and Biological Rhythms · doi:10.1111/j.1479-8425.2005.00168.x · Cited by 15
Murck, H., Frieboes, R.-M., Schier, T., & Steiger, A. (1997) · Pharmacopsychiatry · doi:10.1055/s-2007-979496 · Cited by 11
Alpha-Helical CRH Exerts CRH Agonistic Effects on Sleep-Endocrine Activity in Humans
Held, K., Antonijevic, I. A., Murck, H., Kunzel, H. E., & Steiger, A. (2005) · Neuropsychobiology · doi:10.1159/000086606 · Cited by 9
Cortisol promotes non-REM sleep in patients with major depression
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Reply to the comment on ‘Melatonin as a hypnotic: Pro’
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CNS-specific overexpression of CRH alters sleep-wake behavior in transgenic mice
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Effects of progesterone on sleep and cognition in healthy postmenopausal women
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Effects of sleep deprivation on ghrelin, ACTH, GH and cortisol secretion in normal controls
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Effects of progesterone on sleep and cognition in healthy postmenopausal women
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Effects of progesterone on sleep and cognition in healthy postmenopausal women
Kluge, M., SCHÜSSLER, P., Dresler, M., Yassouridis, A., Held, K., Zihl, J., & Steiger, A. (2006) · Max Planck Institute for Plasma Physics · Cited by 1
Research works printed but not linked: 1
- Künzel, 2000, Impaired sleep in male to female transsexual patients treated with estrogens, Experimental and Clinical Endocrinology & Diabetes, 108, S93
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Metadata
- Authors
- Steiger, A.
- Affiliations
- Max Planck Institute of Psychiatry (DE)
- Corresponding author
- Steiger, Axel
- ORCID
- Steiger, Axel
- Venue
- Journal of Psychiatric Research
- Publisher
- Elsevier BV
- Published
- 2007-10
- Volume
- 41
- Issue
- 7
- Pages
- 537-552
- ISSN
- 0022-3956 (ISSN-L)
- OpenAlex
- W2060446870
- Cited by
- 262
- References
- 188
- Citations by year
- 2026: 4 · 2025: 15 · 2024: 10 · 2023: 8 · 2022: 5 · 2021: 19 · 2020: 10 · 2019: 9 · 2018: 9 · 2017: 5 · 2016: 7 · 2015: 11 · 2014: 14 · 2013: 18 · 2012: 20
- FWCI
- 7.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Psychiatric Research (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- sleep regulation, neuropeptides, growth hormone-releasing hormone, corticotropin-releasing factor, somatostatin, ghrelin, galanin, neuropeptide Y, vasoactive intestinal peptide, neurosteroids, cortisol, estrogen, menopause, GABA-A receptor agonists, gaboxadol, tiagabine, benzodiazepines, REM sleep, slow-wave sleep, depression, aging
- MeSH terms
- Tiagabine, Brain, Corticotropin-Releasing Hormone, Electroencephalography, Estrogens, Humans, Hypnotics and Sedatives, Hypothalamo-Hypophyseal System, Sleep Initiation and Maintenance Disorders, Isoxazoles, Neuropeptides, Nipecotic Acids, Pituitary-Adrenal System, Sleep Stages, Growth Hormone-Releasing Hormone, GABA Agonists, Hormone Replacement Therapy, GABA-A Receptor Agonists
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