Effects of Intravenous Corticotropin-Releasing Hormone upon Sleep-Related Growth Hormone Surge and Sleep EEG in Man
Abstract
Corticotropin-releasing hormone (CRH) plays a key role in coordinating neuroendocrine, metabolic and behavioral responses in stress and affective disorders. To further investigate the effects of enhanced pituitary-adrenocortical activity upon sleep-related phenomena we administered four intravenous injections of 50 µg human (h)-CRH or saline to 11 normal males at 10 p.m., 11 p.m., 12 p.m. and 1 a.m. and measured plasma levels of cortisol and growth hormone (GH) as well as sleep EEG recordings throughout the night. Treatment with h-CRH resulted in a significant increase of mean (± SEM) cortisol secretion between 11 p.m. and 3 a.m. (h-CRH: 100.6 + 9.5 ng/ml; saline: 39.0 ± 1.5 ng/ml; p < 0.01). This initial cortisol increase after repeated h-CRH stimulations was followed by a period of attenuated plasma cortisol between 3 and 7 a.m. (h-CRH: 70.3 + 7.0 ng/ml; saline: 115.5 ± 8.0 ng/ml; p < 0.01). Cortisol surges after h-CRH were associated with a significant blunting of sleep-related GH release expressed as areas under concentration curves (h-CRH: 1.245 ± 0.32 ng/ml/min · 103; saline: 2.462 + 0.92 ng/ml/min· 103, p < O.01). In addition to these hormonal effects, h-CRH induced a decrease of REM and slow wave sleep (stages III and IV) while the amount of more shallow sleep (stages I and II)increased. These effects upon sleep structure were more pronounced during the second part of the night. We conclude that h-CRH induces effects in healthy humans (GH blunting and SWS reduction) which resemble those seen among hypercortisolemic depressives and surmise that CRH plays a role to mediate endocrine as well as behavioral phenomena in the affective disorders.
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There is strong evidence that elevated CRH tone increases sleep EEG frequency, thereby decreasing SWS, and increasing light sleep and wakefulness.
“there is in turn strong evidence that elevated CRH tone increases sleep EEG frequency, thereby decreasing SWS, and increasing light sleep and wakefulness [94].”
From Impact of Sleep and Its Disturbances on Hypothalamo-Pituitary-Adrenal Axis Activity (2010) · cites this paper as [94]
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“It is beyond the scope of this study to reveal whether the decreased amounts of NREM sleep can be attributed to attenuated levels of SWA, but this would implicate that reduced SWA is an intrinsic sleepphysiological feature of the HR mouse line, which might be brought about by a chronic activation of the CRH system [6,…”
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“…studies have shown that CRH has similar effects on sleep and neuroendocrine measures as SP as demonstrated here, i.e. decrease of REM and increase of stage 1 and 2 sleep as well as increase of cortisol secretion and blunting of sleep-related GH release (Born et al. 1989; Holsboer et al. 1988).”
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“In young male healthy volunteers repetitive hourly iv injection from 2200 to 0100 h decrease SWS and the GH surge whereas cortisol levels increase during the first half of the night (Holsboer et al., 1988).”
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“CRH was shown to increase wakefulness (Vgontzas et al., 2001) and to decrease SWS and REM sleep in men (Holsboer et al., 1988) and to decrease sleep 3 stage in women (Schüssler et al., 2008a).”
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Antonijevic, I. A., Murck, H., Frieboes, R.-M., Holsboer, F., & Steiger, A. (1999) · Neuroendocrinology · doi:10.1159/000054487 · Cited by 63 · see citing works
Self-citationListening to mutant mice: a spotlight on the role of CRF/CRF receptor systems in affective disorders
Keck, M. E., Ohl, F., Holsboer, F., & Müller, M. B. (2005) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2005.03.003 · Cited by 62 · see citing works
Self-citationSteiger, A., von Bardeleben, U., Wiedemann, K., & Holsboer, F. (1991) · Journal of Psychiatric Research · doi:10.1016/0022-3956(91)90021-2 · Cited by 61 · see citing works
Self-citationPathology of Sleep, Hormones and Depression
Steiger, A., Dresler, M., Kluge, M., & SCHÜSSLER, P. (2013) · Pharmacopsychiatry · doi:10.1055/s-0033-1337921 · Cited by 61 · see citing works
Self-citationSeelig, E., Keller, U. B., Klarhöfer, M., Scheffler, K., Brand, S., Holsboer‐Trachsler, E., Hatzinger, M., & Bilz, S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0061780 · Cited by 60 · see citing works
“It is well known that corticotropin-releasing hormone and cortisol have adverse effects on sleep quality [24,25].”
BackgroundEnhanced Slow Wave Sleep in Patients with Prolactinoma
Frieboes, R.-M., Murck, H., Stalla, G. K., Antonijevic, I. A., & Steiger, A. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.83.8.5016 · Cited by 66 · see citing works
Self-citationCorticotropin releasing factor receptor antagonists for major depressive disorder
Páez-Pereda, M., Hausch, F., & Holsboer, F. (2011) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2011.565330 · Cited by 59 · see citing works
“These results are in line with the effects on sleep EEG produced by the overexpression of CRF in mice and the intravenous injection of CRF in men [105,106].”
ResultSelf-citationKluge, M., SCHÜSSLER, P., Bleninger, P., Kleyer, S., Uhr, M., Weikel, J. C., Yassouridis, A., Zuber, V., & Steiger, A. (2008) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2008.01.008 · Cited by 56 · see citing works
“The latter finding is in accordance with a significant reduction of REM sleep after CRH administration during spontaneous sleep (Holsboer et al., 1988; Vgontzas et al., 2001).”
BackgroundResultInfluentialSelf-citationSleep disturbances in patients with Addison's disease
Løvås, K., Husebye, E., Holsten, F., & Bjorvatn, B. (2003) · European Journal of Endocrinology · doi:10.1530/eje.0.1480449 · Cited by 55 · see citing works
Cholinergic REM sleep induction test in subjects at high risk for psychiatric disorders
Schreiber, W., Lauer, C. J., Krumrey, K., Holsboer, F., & Krieg, J.-C. (1992) · Biological Psychiatry · doi:10.1016/0006-3223(92)90144-o · Cited by 55 · see citing works
Self-citationThe stress hormone system in various sleep disorders
Lattova, Z., Keckeis, M., Maurovich-Horvat, E., Wetter, T. C., Wilde-Frenz, J., Schuld, A., & Pollmächer, T. (2011) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2011.03.013 · Cited by 54 · see citing works
“Exogenous CRHhas been shown to increase EEG frequency, light sleep and wakefulness (Ehlers et al., 1986; Chang and Opp, 2001) to enhance REM sleep (Kimura et al., 2010) and to decrease the amount of slowwave sleep (SWS;Holsboer et al.,1988).”
BackgroundEndotoxin Enhances EEG Alpha and Beta Power in Human Sleep
Trachsel, L., Schreiber, W., Holsboer, F., & Pollmächer, T. (1994) · SLEEP · doi:10.1093/sleep/17.2.132 · Cited by 54 · see citing works
Self-citationRestless legs syndrome: Evidence for nocturnal hypothalamic‐pituitary‐adrenal system activation
Schilling, C., Schredl, M., Strobl, P., & Deuschle, M. (2010) · Movement Disorders · doi:10.1002/mds.23026 · Cited by 53 · see citing works
Sleep disturbances in highly stress reactive mice: Modeling endophenotypes of major depression
Fenzl, T., Touma, C., Romanowski, C. P. N., Ruschel, J., Holsboer, F., Landgraf, R., Kimura, M., & Yassouridis, A. (2011) · BMC Neuroscience · doi:10.1186/1471-2202-12-29 · Cited by 52 · see citing works
“The locus coeruleus (LC), as part of the reticular activating system projects to the thalamus (additionally to the forebrain, cortex and hypothalamus) and activation through CRH leads to an increase in EEG frequency, decreased SWS (0.5-4.5 Hz) and increased wakefulness [71,72].”
BackgroundInfluentialSelf-citationFrieboes, R.-M., Müller, U., Murck, H., von Cramon, D. Y., Holsboer, F., & Steiger, A. (1999) · Journal of Neuropsychiatry · doi:10.1176/jnp.11.3.354 · Cited by 52 · see citing works
Self-citationHori, H., Teraishi, T., Sasayama, D., Ozeki, Y., Matsuo, J., Kawamoto, Y., Kinoshita, Y., Hattori, K., Higuchi, T., & Kunugi, H. (2011) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2011.04.001 · Cited by 52 · see citing works
Lancel, M., Müller-Preuss, P., Wigger, A., Landgraf, R., & Holsboer, F. (2002) · Journal of Psychiatric Research · doi:10.1016/s0022-3956(02)00009-2 · Cited by 50 · see citing works
Self-citation
- Authors
- Holsboer, F., von Bardeleben, U., & Steiger, A.
- Affiliations
- Johannes Gutenberg University Mainz (DE)
- Venue
- Neuroendocrinology
- Publisher
- S. Karger AG
- Published
- 2008-04-02
- Volume
- 48
- Issue
- 1
- Pages
- 32-38
- ISSN
- 0028-3835 (ISSN-L)
- 1423-0194
- OpenAlex
- W2040727780
- Cited by
- 255
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 7 · 2023: 2 · 2022: 6 · 2021: 11 · 2020: 3 · 2019: 3 · 2018: 1 · 2017: 3 · 2016: 3 · 2015: 6 · 2014: 7 · 2013: 6 · 2012: 2
- FWCI
- 5.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- corticotropin-releasing factor, cortisol secretion, sleep EEG, REM sleep, slow-wave sleep, sleep architecture, growth hormone secretion, circadian rhythm
- MeSH terms
- Adult, Corticotropin-Releasing Hormone, Electroencephalography, Humans, Injections, Intravenous, Male, Pituitary-Adrenal System, Sleep, Growth Hormone
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