A mathematical model of the regulation system of the secretion of glucocorticoids

A mathematical model of the regulation system of the secretion of glucocorticoids

Model Status

This CellML model is known to run in PCEnv and COR and can recreate the published results. ValidateCellML verifies this model as valid CellML, with fully consistent units.

Model Structure

The hypothalamic pituitary adrenal (HPA) axis represents a neuroendocrine system which plays an essential role in maintaining body homeostasis in response to stress. These stresses can be physical (e.g. infection) or psychological (e.g. fear), and both activate the hypothalamus to secrete corticotropin releasing hormone (CRF or CRH). In turn, the presence of CRF in the circulation stimulates the pituitary to release adrenocorticotropic hormone (ACTH) into the blood, where it travels to the adrenal glands and induces the secretion of cortisol from the adrenal cortex. Cortisol has a negative feedback effect on the hypothalamus and pituitary such that the secretion of CRF and ACTH are inhibited.

Cortisol has a number of important cellular and physiological functions, including:

  • inflammation suppression;

  • hormone secretion inhibition; and

  • the induction of lymphocyte apoptosis.

This wide range of effects of cortisol require the feedback loops of the HPA axis to be tightly regulated, and HPA axis disregulation is known to be a feature of numerous stress-related diseases.

Research on the HPA axis function has been hampered by the complexity of its influence on numerous systems. To better understand the function of the HPA axis it has become the subject of several mathematical models, including the model described here in CellML which was published by Bingzheng et al. in 1990 (see the figure below). Model simulation data compared well with experimental results, but it was agreed that the model required some further refinement to perfectly recreate the physiological situation.

The complete original paper reference is cited below:

A mathematical model of the regulation system of the secretion of glucocorticoids, Liu Bingzheng, Zhao Zhenye and Chen Liansong, 1990, Journal of Biological Physics, volume 17, issue 4, 221-233.

The HPA axis model has three compartments, namely the hypothalamus, pituitary and adrenals. Neural signals trigger CRF secretion by the hypothalamus. In turn, this signals to the pituitary to release ACTH which stimulates the adrenal gland to release cortisol. Cortisol acts on the hypothalamus and the pituitary to have a negative feedback effect on the release of CRH and ACTH respectively.