Predictive modeling of the hypothalamic-pituitary-adrenal (HPA) axis response to acute and chronic stress
Апстракт
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.
Кључне речи:
HPA axis / Stress / Cortisol / Predictive modeling / Circadian and ultradian rhythmicityИзвор:
Endocrine Journal, 2011, 58, 10, 889-904Издавач:
- Japan Endocrine Soc, Kyoto
Финансирање / пројекти:
- Динамика нелинеарних физичкохемијских и биохемијских система са моделирањем и предвиђањем њихових понашања под неравнотежним условима (RS-172015)
- Наноструктурни функционални и композитни материјали у каталитичким и сорпционим процесима (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
Институција/група
IHTMTY - 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 . .