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

Autor: Ljiljana Kolar-Anić, Vladimir M. Marković, Vladana Vukojević, Zeljko Cupic
Rok vydání: 2011
Předmět:
Activity Cycles
Metabolic load
Hypothalamo-Hypophyseal System
medicine.medical_specialty
endocrine system
Endocrinology
Diabetes and Metabolism
Pituitary-Adrenal System
Stress
Circadian and ultradian rhythmicity
Models
Biological
Cortisol
03 medical and health sciences
0302 clinical medicine
Endocrinology
Adrenal Cortex Hormones
Stress
Physiological
Internal medicine
Animals
Humans
Medicine
Computer Simulation
Chronic stress
Circadian rhythm
Glucocorticoids
Cortisol level
030304 developmental biology
Ultradian rhythm
0303 health sciences
Hypothalamic Hormones
business.industry
HPA axis
Predictive modeling
Circadian Rhythm
Intensity (physics)
Pituitary Hormones
Bifurcation analysis
Acute Disease
Chronic Disease
business
Stress
Psychological
030217 neurology & neurosurgery
Overall status
hormones
hormone substitutes
and hormone antagonists
Zdroj: Endocrine Journal
Karolinska Institutet
Popis: Detailed dynamics of the hypothalamic-pituitary-adrenal (HPA) 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.
Databáze: OpenAIRE
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