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The Pulsatile Characteristics of Hypothalamo-Pituitary-Adrenal Activity in Female Lewis and Fischer 344 Rats and Its Relationship to Differential Stress Responses*
Abstract
The dynamic patterns of basal and stimulated hypothalamo-pituitary-adrenal (HPA) activity of freely moving female Lewis and Fischer 344 rats were compared using an automated blood-sampling system. Both strains showed pulsatile corticosterone release throughout the 24 h cycle. Lewis rats showed clear circadian variation in both pulse frequency (8.4 +/- 0.4 pulses between 1700-2300 h vs. 5.3 +/- 0.8 pulses between 0500-1100 h; P < 0.05) and height (198 +/- 27 ng/ml between 1700-2300 h vs. 107 +/- 14 ng/ml between 0500-1100 h; P < 0.05). Fischer rats exhibited pulses of similar frequency and height to those in Lewis rats during the evening, but showed no circadian variation, resulting in higher mean daily corticosterone concentrations. Although both strains showed behavioral and HPA responses to white noise stress (10 min; 114 dB), Fischer rats showed much greater increases in total activity, grooming, and rearings, and two important differences in the corticosterone responses were observed. First, in Lewis rats a clear relationship existed between basal and stimulated HPA activities, in that a significant response was seen only when the stress coincided with the rising (secretory active) phase of a basal pulse. Noise stress coinciding with a falling (nonsecretory) phase elicited no significant response. In contrast, Fischer rats showed similar responses regardless of the underlying pulse phase. Second, after the peak response at 20 min (Lewis, 237 +/- 67 ng/ml; Fischer, 390 +/- 57 ng/ml), corticosterone levels fell rapidly in Lewis rats, but remained maximally elevated for 20 min in Fischer rats, resulting in a significantly greater integrated response. The corticosterone response to i.v. CRF was unaffected by pulse phase in both strains, suggesting that a suprapituitary mechanism mediates the phase-dependent response to stress in the Lewis strain. CRF-induced corticosterone levels rose more rapidly in Fischer rats, peaking at 10 min (473 +/- 95 ng/ml) compared with 30 min (390 +/- 75 ng/ml) in Lewis rats, suggesting greater pituitary sensitivity in this strain. Thus, differences in both central and pituitary control of the HPA axis contribute to the strain difference in stress responsiveness between female Lewis and Fischer rats.
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“the timing of an incoming stressor, relative to the phase of an endogenous pulse of CORT, has been shown to govern the amplitude of the subsequent stress response as well as the timing of subsequent pulses [1,12].”
From Rapid intra-adrenal feedback regulation of glucocorticoid synthesis (2015) · cites this paper as [1]
In the citing paper
“new experimental [9-15] and theoretical [16-27] results offer enough evidence to support the indispensable roles of ultradian oscillatory dynamics of HPA hormones levels for normal physiology.”
From Predictive modeling of the hypothalamic-pituitary-adrenal (HPA) axis response to acute and chronic stress (2011) · cites this paper as [14]
In the citing paper
“the same acute stress (5 min white noise stress of 114 dB) applied either in the ascending (secreting) and interpulse phase or during the descending (non-secreting) phase of corticosterone ultradian rhythm evoked significant increase of corticosterone level only when it had been applied during the ascending [13-15] or interpulse [15] phase of ultradian basal corticosterone pulse.”
From Predictive modeling of the hypothalamic-pituitary-adrenal (HPA) axis response to acute and chronic stress (2011) · cites this paper as [14]
In the citing paper
“there are several experimental observa -tions showing that acute stress induces different effects depending on the phase of the ultradian secretion pulse at which the stress has been induced [11, 13-15].”
From Predictive modeling of the hypothalamic-pituitary-adrenal (HPA) axis response to acute and chronic stress (2011) · cites this paper as [14]
In the citing paper
“according to which the HPA axis response to stress depends on the ultradian phase (Fig. 2)”
From Predictive modeling of the hypothalamic-pituitary-adrenal (HPA) axis response to acute and chronic stress (2011) · cites this paper as [14]
In the citing paper
“intravenous injection of specific dosage of CRH (2 μg) administered to rats during the rising or falling phase of the corticosterone ultradian oscillations failed to induce significant difference between the two rat groups [14].”
From Predictive modeling of the hypothalamic-pituitary-adrenal (HPA) axis response to acute and chronic stress (2011) · cites this paper as [14]
In the citing paper
“Numerical simulations (Figs. 2, 3) reproduced the empirically well established notion that the same stimulus applied at slightly different time points, may induce different, even opposite changes in cortisol levels in the same individual [13-15].”
From Predictive modeling of the hypothalamic-pituitary-adrenal (HPA) axis response to acute and chronic stress (2011) · cites this paper as [14]
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Metadata
- Authors
- Windle, R. J., Wood, S. A., Lightman, S. L., & Ingram, C. D.
- Affiliations
- Bristol Royal Infirmary (GB)
- University of Bristol (GB)
- Corresponding author
- Windle, R. J.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 1998-10-01
- Volume
- 139
- Issue
- 10
- Pages
- 4044-4052
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W1987343103
- Cited by
- 201
- References
- 52
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 9 · 2019: 9 · 2018: 2 · 2017: 4 · 2016: 10 · 2015: 6 · 2014: 8 · 2013: 6 · 2012: 8
- FWCI
- 2.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- hypothalamic-pituitary-adrenal axis, circadian variation, corticotropin-releasing factor, strain differences, Lewis rats, F344 rats, female rats, behavioral stress response, automated blood sampling
- MeSH terms
- Animals, Circadian Rhythm, Corticosterone, Corticotropin-Releasing Hormone, Female, Hypothalamo-Hypophyseal System, Pituitary-Adrenal System, Rats, Inbred F344, Rats, Inbred Lew, Species Specificity, Stress, Physiological, Rats
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