The significance of glucocorticoid pulsatility
Abstract
Glucocorticoids are secreted in discrete pulses resulting in an ultradian rhythm in all species that have been studied. In the rat there is an approximately hourly rhythm of corticosterone secretion, which appears to be regulated by alternating activation and inhibition of the HPA axis. At the level of signal transduction, the response to these pulses of corticosterone is determined by its dynamic interaction with the two transcription factors--the glucocorticoid and mineralocorticoid receptors. While the mineralocorticoid receptor remains activated throughout the ultradian cycle, the glucocorticoid receptor shows a phasic response to each individual pulse of corticosterone. This phasic response is regulated by an intranuclear proteasome-dependent rapid downregulation of the activated glucocorticoid receptor.
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Pulsatility of glucocorticoid secretion is an important factor in determining the responsivity of the HPA axis to stress.
“This pulsatility of glucocorticoid secretion is also an important factor in determining the responsivity of the HPA axis to stress (Windle et al. 1998a; Lightman et al. 2008) and the transcriptional responses of glucocorticoid responsive genes (Stavreva et al. 2009).”
From Origin of ultradian pulsatility in the hypothalamic–pituitary–adrenal axis (2010) · cites this paper as Lightman et al. 2008
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References 70 · Cited by 241
- Authors
- Lightman, S. L., Wiles, C. C., Atkinson, H. C., Henley, D. E., Russell, G. M., Leendertz, J. A., McKenna, M. A., Spiga, F., Wood, S. A., & Conway-Campbell, B. L.
- Affiliations
- University of Bristol (GB)
- Corresponding author
- Lightman, Stafford L.
- ORCID
- Venue
- European Journal of Pharmacology
- Publisher
- Elsevier BV
- Published
- 2008-04
- Volume
- 583
- Issue
- 2-3
- Pages
- 255-262
- ISSN
- 0014-2999 (ISSN-L)
- OpenAlex
- W2094075153
- Cited by
- 241
- References
- 70
- Citations by year
- 2026: 12 · 2025: 5 · 2024: 9 · 2023: 7 · 2022: 12 · 2021: 10 · 2020: 10 · 2019: 7 · 2018: 14 · 2017: 15 · 2016: 14 · 2015: 11 · 2014: 15 · 2013: 11 · 2012: 22
- FWCI
- 1.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Bristol Research (University of Bristol) (publishedVersion)
- Funders
- Wellcome Trust (074112)
- Biotechnology and Biological Sciences Research Council (BB/C51297X/1)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- ultradian rhythms, corticosterone secretion, hypothalamic-pituitary-adrenal axis, glucocorticoid receptor, mineralocorticoid receptor, receptor down-regulation, proteasome, signal transduction, glucocorticoid signaling
- MeSH terms
- Activity Cycles, Animals, Glucocorticoids, Humans, Hypothalamo-Hypophyseal System, Pituitary-Adrenal System, Stress, Physiological, Time Factors, Signal Transduction, Rats
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