Modeling robust oscillatory behavior of the hypothalamic-pituitary-adrenal axis

Modeling robust oscillatory behavior of the hypothalamic-pituitary-adrenal axis

Model Status

This CellML model runs in OpenCell, PCEnv and COR, and the units are consistent throughout. The model does not quite recreate the published results (although the output is similar), part of the reason for this might be that the original model uses reset rules to define injections of additional hormones, which is not a supported feature in CellML at present.

Model Structure

ABSTRACT: A mathematical model of the hypothalamic-pituitary-adrenal (HPA) axis of the human endocrine system is proposed. This new model provides an improvement over previous models by introducing two nonlinear factors with physiological relevance: 1) a limit to gland size; 2) rejection of negative hormone concentrations. The result is that the new model is by far the most robust; e.g., it can tolerate at least -50% and +100% perturbations to any of its parameters. This high degree of robustness allows one, for the first time, to model features of the system such as circadian rhythm and response to hormone injections. In addition, relative to its closest predecessor, the model is simpler; it contains only about half of the parameters, and yet achieves more functions. The new model provides opportunities for teaching endocrinology within a biological or medical school context; it may also have applications in modeling and studying HPA axis disorders, for example, related to gland size dynamics, abnormal hormone levels, or stress influences.

Schematic diagram of the hypothalamus-pituitary-adrenal (HPA) axis. Stimulatory and inhibitory paths are indicated by the arrows and + or - signs respectively. CRH represents corticotropin-releasing hormone, ACTH is corticotropin, and CBG represents corticosteroid-binding globulin.

The original paper reference is cited below:

Modeling robust oscillatory behavior of the hypothalamic-pituitary-adrenal axis, Vadim Kyrylov, Liudmila A. Severyanova, and Amandio Vieira, 2005, IEEE Transactions on Biomedical Engineering, 52, 1977-1983. PubMed ID: 16366221