Characterizing dynamic interactions between ultradian glucocorticoid rhythmicity and acute stress using the phase response curve.

The hypothalamic-pituitary-adrenal (HPA) axis is a dynamic oscillatory hormone signalling system that regulates the pulsatile secretion of glucocorticoids from the adrenal glands. In addition to regulation of basal levels of glucocorticoids, the HPA axis provides a rapid hormonal response to stress...

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Main Authors: James Rankin, Jamie J Walker, Richard Windle, Stafford L Lightman, John R Terry
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0030978&type=printable
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author James Rankin
Jamie J Walker
Richard Windle
Stafford L Lightman
John R Terry
author_facet James Rankin
Jamie J Walker
Richard Windle
Stafford L Lightman
John R Terry
author_sort James Rankin
collection DOAJ
description The hypothalamic-pituitary-adrenal (HPA) axis is a dynamic oscillatory hormone signalling system that regulates the pulsatile secretion of glucocorticoids from the adrenal glands. In addition to regulation of basal levels of glucocorticoids, the HPA axis provides a rapid hormonal response to stress that is vitally important for homeostasis. Recently it has become clear that glucocorticoid pulses encode an important biological signal that regulates receptor signalling both in the central nervous system and in peripheral tissues. It is therefore important to understand how stressful stimuli disrupt the pulsatile dynamics of this system. Using a computational model that incorporates the crucial feed-forward and feedback components of the axis, we provide novel insight into experimental observations that the size of the stress-induced hormonal response is critically dependent on the timing of the stress. Further, we employ the theory of Phase Response Curves to show that an acute stressor acts as a phase-resetting mechanism for the ultradian rhythm of glucocorticoid secretion. Using our model, we demonstrate that the magnitude of an acute stress is a critical factor in determining whether the system resets via a Type 1 or Type 0 mechanism. By fitting our model to our in vivo stress-response data, we show that the glucocorticoid response to an acute noise stress in rats is governed by a Type 0 phase-resetting curve. Our results provide additional evidence for the concept of a deterministic sub-hypothalamic oscillator regulating the ultradian glucocorticoid rhythm, which constitutes a highly responsive peripheral hormone system that interacts dynamically with hypothalamic inputs to regulate the overall hormonal response to stress.
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spelling doaj-art-d18ea064b6194ec9a201735e13f7c1ae2025-08-20T02:05:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0172e3097810.1371/journal.pone.0030978Characterizing dynamic interactions between ultradian glucocorticoid rhythmicity and acute stress using the phase response curve.James RankinJamie J WalkerRichard WindleStafford L LightmanJohn R TerryThe hypothalamic-pituitary-adrenal (HPA) axis is a dynamic oscillatory hormone signalling system that regulates the pulsatile secretion of glucocorticoids from the adrenal glands. In addition to regulation of basal levels of glucocorticoids, the HPA axis provides a rapid hormonal response to stress that is vitally important for homeostasis. Recently it has become clear that glucocorticoid pulses encode an important biological signal that regulates receptor signalling both in the central nervous system and in peripheral tissues. It is therefore important to understand how stressful stimuli disrupt the pulsatile dynamics of this system. Using a computational model that incorporates the crucial feed-forward and feedback components of the axis, we provide novel insight into experimental observations that the size of the stress-induced hormonal response is critically dependent on the timing of the stress. Further, we employ the theory of Phase Response Curves to show that an acute stressor acts as a phase-resetting mechanism for the ultradian rhythm of glucocorticoid secretion. Using our model, we demonstrate that the magnitude of an acute stress is a critical factor in determining whether the system resets via a Type 1 or Type 0 mechanism. By fitting our model to our in vivo stress-response data, we show that the glucocorticoid response to an acute noise stress in rats is governed by a Type 0 phase-resetting curve. Our results provide additional evidence for the concept of a deterministic sub-hypothalamic oscillator regulating the ultradian glucocorticoid rhythm, which constitutes a highly responsive peripheral hormone system that interacts dynamically with hypothalamic inputs to regulate the overall hormonal response to stress.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0030978&type=printable
spellingShingle James Rankin
Jamie J Walker
Richard Windle
Stafford L Lightman
John R Terry
Characterizing dynamic interactions between ultradian glucocorticoid rhythmicity and acute stress using the phase response curve.
PLoS ONE
title Characterizing dynamic interactions between ultradian glucocorticoid rhythmicity and acute stress using the phase response curve.
title_full Characterizing dynamic interactions between ultradian glucocorticoid rhythmicity and acute stress using the phase response curve.
title_fullStr Characterizing dynamic interactions between ultradian glucocorticoid rhythmicity and acute stress using the phase response curve.
title_full_unstemmed Characterizing dynamic interactions between ultradian glucocorticoid rhythmicity and acute stress using the phase response curve.
title_short Characterizing dynamic interactions between ultradian glucocorticoid rhythmicity and acute stress using the phase response curve.
title_sort characterizing dynamic interactions between ultradian glucocorticoid rhythmicity and acute stress using the phase response curve
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0030978&type=printable
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