Amplitude modulation of a burstlike mode of cortisol secretion subserves the circadian glucocorticoid rhythm
Abstract
We have examined the mechanism subserving the in vivo circadian rhythm of cortisol in men. To this end, blood samples were withdrawn at 10-min intervals for 24 h in each of six men to yield well-defined profiles of episodic cortisol release. A novel multiple-parameter deconvolution model was applied to discriminate the number, amplitudes, and durations of all statistically significant underlying cortisol secretory bursts from the plasma hormone concentrations and simultaneously estimate the endogenous half-life of cortisol disappearance in each subject. These experiments disclosed randomly occurring cortisol secretory bursts at a mean frequency of 19 +/- 0.82 events per day (interpulse interval 77 +/- 4.0 min). Secretory bursts exhibited a mean half-duration (duration at half-maximal amplitude) of only 16 +/- 0.61 min indicating that 95% of daily cortisol secretion occurred in 8.2 h. Cortisol secretory burst frequency varied 2.2-fold over 24 h, whereas cortisol secretory burst amplitude varied 6.6-fold. We conclude that the nyctohemeral pattern of cortisol variation in vivo can be accounted for by an amplitude-modulated, random burstlike mode of cortisol secretion without the need to postulate a tonic mode of cortisol release.
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HPA axis activity is characterized by a classic circadian rhythm and an ultradian pattern of discrete pulsatile glucocorticoid release.
“The activity of the HPA axis is characterized not only by a classic circadian rhythm, but also by an ultradian pattern of discrete pulsatile release of glucocorticoids.”
From Origin of ultradian pulsatility in the hypothalamic–pituitary–adrenal axis (2010) · cites this paper as Veldhuis et al. 1989
Changes in pulse amplitude, and to a lesser extent frequency, make up the circadian rhythm and the changes of HPA activity in response to altered physiological and pathological conditions.
“It is in fact the changes in pulse amplitude, and to a lesser extent frequency, that make up the circadian rhythm (Lui et al. 1987; Iranmanesh et al. 1989; Veldhuis et al. 1989, 1990; Windle et al. 1998b) and the changes of HPA activity that occur in response to altered physiological and pathological conditions.”
From Origin of ultradian pulsatility in the hypothalamic–pituitary–adrenal axis (2010) · cites this paper as Veldhuis et al. 1989
Persistent ultradian oscillations arise from other mechanisms than the minimal model.
“This suggests that persistent ultradian oscillations arise from other mechanisms [26, 25, 49].”
From Patient specific modeling of the HPA axis related to clinical diagnosis of depression (2017) · cites this paper as [49]
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“However, an ultradian rhythm has been identified, characterized by a more rapid pulsatile glucocorticoid secretion occurring on top of the circadian rhythm [ 34–37].”
- Authors
- Veldhuis, J. D., Iranmanesh, A., Lizarralde, G., & Johnson, M. L.
- Affiliations
- University of Virginia Medical Center (US)
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 1989-07-01
- Volume
- 257
- Issue
- 1
- Pages
- E6-E14
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W181028834
- Cited by
- 224
- References
- 0
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 5 · 2023: 4 · 2022: 5 · 2021: 8 · 2020: 6 · 2019: 9 · 2018: 10 · 2017: 7 · 2016: 8 · 2015: 8 · 2014: 11 · 2013: 10 · 2012: 4
- FWCI
- 2.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5k04hd000634-02, AM30302)
- National Center for Research Resources (RR 00847)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (1-K04-HD-00634)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- cortisol secretion, circadian rhythm, amplitude modulation, deconvolution model, nyctohemeral rhythm, plasma cortisol
- MeSH terms
- Adult, Circadian Rhythm, Half-Life, Humans, Hydrocortisone, Male, Middle Aged, Periodicity, Regression Analysis
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