title: Modelling cholesterol effects on the dynamics of the hypothalamic-pituitary-adrenal (HPA) axis.
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.
authors.affiliation: Faculty of Physical Chemistry, University of Belgrade, Studentski trg 12-16, 11000 Belgrade, Serbia vmarkovic@ffh.bg.ac.rs.
authors.forename: Vladimir M
authors.initials: VM
authors.lastname: Marković
authors.affiliation: Department of Catalysis and Chemical Engineering, Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Njegoševa 12, 11000 Belgrade, Serbia.
authors.forename: Željko
authors.initials: Ž
authors.lastname: Čupić
authors.affiliation: Faculty of Physical Chemistry, University of Belgrade, Studentski trg 12-16, 11000 Belgrade, Serbia.
authors.forename: Stevan
authors.initials: S
authors.lastname: Maćešić
authors.affiliation: Faculty of Physical Chemistry, University of Belgrade, Studentski trg 12-16, 11000 Belgrade, Serbia.
authors.forename: Ana
authors.initials: A
authors.lastname: Stanojević
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine CMM L8:01, 17176 Stockholm, Sweden vladana.vukojevic@ki.se.
authors.forename: Vladana
authors.initials: V
authors.lastname: Vukojević
authors.affiliation: Faculty of Physical Chemistry, University of Belgrade, Studentski trg 12-16, 11000 Belgrade, Serbia and Department of Catalysis and Chemical Engineering, Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Njegoševa 12, 11000 Belgrade, Serbia.
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Kolar-Anić
mesh_terms: D002784:Cholesterol / Q000378:metabolism*; D002940:Circadian Rhythm / Q000502:physiology*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D008962:Models, Theoretical; D010913:Pituitary-Adrenal System / Q000378:metabolism*; D000071218:Ultradian Rhythm / Q000502:physiology*
chemical_list: D002784:Cholesterol
keywords: Cholesterol; Hypothalamic–pituitary–adrenal (HPA) axis; circadian and ultradian rhythms; cortisol; dynamical diseases; stoichiometric network analysis