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Predictive modeling of the hypothalamic-pituitary-adrenal (HPA) axis response to acute and chronic stress

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2011
777.pdf (1.367Mb)
Authors
Marković, Vladimir M.
Čupić, Željko
Vukojevic, Vladana
Kolar-Anić, Ljiljana
Article (Published version)
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Abstract
Detailed dynamics of the hypothalamic-pituitary-adrenal (I-IPA) axis is complex, depending on the individual metabolic load of an organism, its current status (healthy/ill, circadian phase (day/night), ultradian phase) and environmental impact. Therefore, it is difficult to compare the HPA axis activity between different individuals or draw unequivocal conclusions about the overall status of the HPA axis in an individual using single time-point measurements of cortisol levels. The aim of this study is to identify parameters that enable us to compare different dynamic states of the HPA axis and use them to investigate self-regulation mechanisms in the HPA axis under acute and chronic stress. In this regard, a four-dimensional stoichiometric model of the HPA axis was used. Acute stress was modeled by inducing an abrupt change in cortisol level during the course of numerical integration, whereas chronic stress was modeled by changing the mean stationary state concentrations of CRH. Effect...s of acute stress intensity, duration and time of onset with respect to the ultradian amplitude, ultradian phase and the circadian phase of the perturbed oscillation were studied in detail. Bifurcation analysis was used to predict the response of the HPA axis to chronic stress. Model predictions were compared with experimental findings reported in the literature and relevance for pharmacotherapy with glucocorticoids was discussed.

Keywords:
HPA axis / Stress / Cortisol / Predictive modeling / Circadian and ultradian rhythmicity
Source:
Endocrine Journal, 2011, 58, 10, 889-904
Publisher:
  • Japan Endocrine Soc, Kyoto
Funding / projects:
  • Dynamics of nonlinear physicochemical and biochemical systems with modeling and predicting of their behavior under nonequilibrium conditions (RS-172015)
  • Nanostructured Functional and Composite Materials in Catalytic and Sorption Processes (RS-45001)
  • Swedish Research Council
  • Swedish Brain Foundation
  • Knut and Alice Wallenberg Foundation

DOI: 10.1507/endocrj.EJ11-0037

ISSN: 0918-8959

PubMed: 21852742

WoS: 000296408600009

Scopus: 2-s2.0-80055071240
[ Google Scholar ]
39
37
URI
https://cer.ihtm.bg.ac.rs/handle/123456789/779
Collections
  • Radovi istraživača / Researchers' publications
Institution/Community
IHTM
TY  - JOUR
AU  - Marković, Vladimir M.
AU  - Čupić, Željko
AU  - Vukojevic, Vladana
AU  - Kolar-Anić, Ljiljana
PY  - 2011
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/779
AB  - Detailed dynamics of the hypothalamic-pituitary-adrenal (I-IPA) axis is complex, depending on the individual metabolic load of an organism, its current status (healthy/ill, circadian phase (day/night), ultradian phase) and environmental impact. Therefore, it is difficult to compare the HPA axis activity between different individuals or draw unequivocal conclusions about the overall status of the HPA axis in an individual using single time-point measurements of cortisol levels. The aim of this study is to identify parameters that enable us to compare different dynamic states of the HPA axis and use them to investigate self-regulation mechanisms in the HPA axis under acute and chronic stress. In this regard, a four-dimensional stoichiometric model of the HPA axis was used. Acute stress was modeled by inducing an abrupt change in cortisol level during the course of numerical integration, whereas chronic stress was modeled by changing the mean stationary state concentrations of CRH. Effects of acute stress intensity, duration and time of onset with respect to the ultradian amplitude, ultradian phase and the circadian phase of the perturbed oscillation were studied in detail. Bifurcation analysis was used to predict the response of the HPA axis to chronic stress. Model predictions were compared with experimental findings reported in the literature and relevance for pharmacotherapy with glucocorticoids was discussed.
PB  - Japan Endocrine Soc, Kyoto
T2  - Endocrine Journal
T1  - Predictive modeling of the hypothalamic-pituitary-adrenal (HPA) axis response to acute and chronic stress
VL  - 58
IS  - 10
SP  - 889
EP  - 904
DO  - 10.1507/endocrj.EJ11-0037
ER  - 
@article{
author = "Marković, Vladimir M. and Čupić, Željko and Vukojevic, Vladana and Kolar-Anić, Ljiljana",
year = "2011",
abstract = "Detailed dynamics of the hypothalamic-pituitary-adrenal (I-IPA) axis is complex, depending on the individual metabolic load of an organism, its current status (healthy/ill, circadian phase (day/night), ultradian phase) and environmental impact. Therefore, it is difficult to compare the HPA axis activity between different individuals or draw unequivocal conclusions about the overall status of the HPA axis in an individual using single time-point measurements of cortisol levels. The aim of this study is to identify parameters that enable us to compare different dynamic states of the HPA axis and use them to investigate self-regulation mechanisms in the HPA axis under acute and chronic stress. In this regard, a four-dimensional stoichiometric model of the HPA axis was used. Acute stress was modeled by inducing an abrupt change in cortisol level during the course of numerical integration, whereas chronic stress was modeled by changing the mean stationary state concentrations of CRH. Effects of acute stress intensity, duration and time of onset with respect to the ultradian amplitude, ultradian phase and the circadian phase of the perturbed oscillation were studied in detail. Bifurcation analysis was used to predict the response of the HPA axis to chronic stress. Model predictions were compared with experimental findings reported in the literature and relevance for pharmacotherapy with glucocorticoids was discussed.",
publisher = "Japan Endocrine Soc, Kyoto",
journal = "Endocrine Journal",
title = "Predictive modeling of the hypothalamic-pituitary-adrenal (HPA) axis response to acute and chronic stress",
volume = "58",
number = "10",
pages = "889-904",
doi = "10.1507/endocrj.EJ11-0037"
}
Marković, V. M., Čupić, Ž., Vukojevic, V.,& Kolar-Anić, L.. (2011). Predictive modeling of the hypothalamic-pituitary-adrenal (HPA) axis response to acute and chronic stress. in Endocrine Journal
Japan Endocrine Soc, Kyoto., 58(10), 889-904.
https://doi.org/10.1507/endocrj.EJ11-0037
Marković VM, Čupić Ž, Vukojevic V, Kolar-Anić L. Predictive modeling of the hypothalamic-pituitary-adrenal (HPA) axis response to acute and chronic stress. in Endocrine Journal. 2011;58(10):889-904.
doi:10.1507/endocrj.EJ11-0037 .
Marković, Vladimir M., Čupić, Željko, Vukojevic, Vladana, Kolar-Anić, Ljiljana, "Predictive modeling of the hypothalamic-pituitary-adrenal (HPA) axis response to acute and chronic stress" in Endocrine Journal, 58, no. 10 (2011):889-904,
https://doi.org/10.1507/endocrj.EJ11-0037 . .

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