Modelling cholesterol effects on the dynamics of the hypothalamic-pituitary-adrenal (HPA) axis

2016
Authors
Marković, Vladimir M.Čupić, Željko

Macesic, Stevan
Stanojevic, Ana
Vukojevic, Vladana
Kolar-Anić, Ljiljana

Article (Published version)

Metadata
Show full item recordAbstract
A mathematical model of the hypothalamic-pituitary-adrenal (HPA) axis with cholesterol as a dynamical variable was derived to investigate the effects of cholesterol, the primary precursor of all steroid hormones, on the ultradian and circadian HPA axis activity. To develop the model, the parameter space was systematically examined by stoichiometric network analysis to identify conditions for ultradian oscillations, determine conditions under which dynamic transitions, i.e. bifurcations occur and identify bifurcation types. The bifurcations were further characterized using numerical simulations. Model predictions agree well with empirical findings reported in the literature, indicating that cholesterol levels may critically affect the global dynamics of the HPA axis. The proposed model provides a base for better understanding of experimental observations, it may be used as a tool for designing experiments and offers useful insights into the characteristics of basic dynamic regulatory me...chanisms that, when impaired, may lead to the development of some modern-lifestyle-associated diseases.
Keywords:
hypothalamic-pituitary-adrenal (HPA) axis / cholesterol / circadian and ultradian rhythms / cortisol / dynamical diseases / stoichiometric network analysisSource:
Mathematical Medicine and Biology-A Journal of the Ima, 2016, 33, 1, 1-28Publisher:
- Oxford Univ Press, Oxford
Funding / projects:
- Karolinska Institute Research Funds
- Swedish Research Council
- Knut and Alice Wallenberg Foundation
- Rajko and Maj Dermanovic Fund
- 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)
DOI: 10.1093/imammb/dqu020
ISSN: 1477-8599
PubMed: 25332212
WoS: 000374232600001
Scopus: 2-s2.0-84963762537
Collections
Institution/Community
IHTMTY - JOUR AU - Marković, Vladimir M. AU - Čupić, Željko AU - Macesic, Stevan AU - Stanojevic, Ana AU - Vukojevic, Vladana AU - Kolar-Anić, Ljiljana PY - 2016 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/1929 AB - A mathematical model of the hypothalamic-pituitary-adrenal (HPA) axis with cholesterol as a dynamical variable was derived to investigate the effects of cholesterol, the primary precursor of all steroid hormones, on the ultradian and circadian HPA axis activity. To develop the model, the parameter space was systematically examined by stoichiometric network analysis to identify conditions for ultradian oscillations, determine conditions under which dynamic transitions, i.e. bifurcations occur and identify bifurcation types. The bifurcations were further characterized using numerical simulations. Model predictions agree well with empirical findings reported in the literature, indicating that cholesterol levels may critically affect the global dynamics of the HPA axis. The proposed model provides a base for better understanding of experimental observations, it may be used as a tool for designing experiments and offers useful insights into the characteristics of basic dynamic regulatory mechanisms that, when impaired, may lead to the development of some modern-lifestyle-associated diseases. PB - Oxford Univ Press, Oxford T2 - Mathematical Medicine and Biology-A Journal of the Ima T1 - Modelling cholesterol effects on the dynamics of the hypothalamic-pituitary-adrenal (HPA) axis VL - 33 IS - 1 SP - 1 EP - 28 DO - 10.1093/imammb/dqu020 ER -
@article{ author = "Marković, Vladimir M. and Čupić, Željko and Macesic, Stevan and Stanojevic, Ana and Vukojevic, Vladana and Kolar-Anić, Ljiljana", year = "2016", abstract = "A mathematical model of the hypothalamic-pituitary-adrenal (HPA) axis with cholesterol as a dynamical variable was derived to investigate the effects of cholesterol, the primary precursor of all steroid hormones, on the ultradian and circadian HPA axis activity. To develop the model, the parameter space was systematically examined by stoichiometric network analysis to identify conditions for ultradian oscillations, determine conditions under which dynamic transitions, i.e. bifurcations occur and identify bifurcation types. The bifurcations were further characterized using numerical simulations. Model predictions agree well with empirical findings reported in the literature, indicating that cholesterol levels may critically affect the global dynamics of the HPA axis. The proposed model provides a base for better understanding of experimental observations, it may be used as a tool for designing experiments and offers useful insights into the characteristics of basic dynamic regulatory mechanisms that, when impaired, may lead to the development of some modern-lifestyle-associated diseases.", publisher = "Oxford Univ Press, Oxford", journal = "Mathematical Medicine and Biology-A Journal of the Ima", title = "Modelling cholesterol effects on the dynamics of the hypothalamic-pituitary-adrenal (HPA) axis", volume = "33", number = "1", pages = "1-28", doi = "10.1093/imammb/dqu020" }
Marković, V. M., Čupić, Ž., Macesic, S., Stanojevic, A., Vukojevic, V.,& Kolar-Anić, L.. (2016). Modelling cholesterol effects on the dynamics of the hypothalamic-pituitary-adrenal (HPA) axis. in Mathematical Medicine and Biology-A Journal of the Ima Oxford Univ Press, Oxford., 33(1), 1-28. https://doi.org/10.1093/imammb/dqu020
Marković VM, Čupić Ž, Macesic S, Stanojevic A, Vukojevic V, Kolar-Anić L. Modelling cholesterol effects on the dynamics of the hypothalamic-pituitary-adrenal (HPA) axis. in Mathematical Medicine and Biology-A Journal of the Ima. 2016;33(1):1-28. doi:10.1093/imammb/dqu020 .
Marković, Vladimir M., Čupić, Željko, Macesic, Stevan, Stanojevic, Ana, Vukojevic, Vladana, Kolar-Anić, Ljiljana, "Modelling cholesterol effects on the dynamics of the hypothalamic-pituitary-adrenal (HPA) axis" in Mathematical Medicine and Biology-A Journal of the Ima, 33, no. 1 (2016):1-28, https://doi.org/10.1093/imammb/dqu020 . .