Modelling cholesterol effects on the dynamics of the hypothalamic-pituitary-adrenal (HPA) axis
AuthorsMarković, Vladimir M.
Article (Published version)
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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 analysis
Source:Mathematical Medicine and Biology-A Journal of the Ima, 2016, 33, 1, 1-28
- Oxford Univ Press, Oxford
- 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)