A computer simulation of the hypothalamic-pituitary-adrenal axis

Model Structure

The hypothalamic-pituitary-adrenal axis (HPA axis) regulates the secretion of cortisol through a complex network of interacting components. Although our knowledge about each of these separate components is increasing, our understanding of how these components are combined into a network, and how this network functions, is still limited. In an attempt to address this issue, mathematical models of the HPA axis are being developed, and represent an informative, valuable, exploratory tool.

The current model described here in CellML is based on the HPA axis model published by Gonzalez-Heydrich et al. (1994) (the complete original paper reference is cited below). The mathematical model simulates components of the HPA axis involved in the continuous secretion and elimination of cortisol, adrenocorticotropin (ACTH), and corticotropin releasing hormone (CRH). The relationships between these components were modelled based on current knowledge of their functioning, and model parameters were derived from experimental results in the published literature. The presence of CRH and arginine-vasopressin (AVP), which are produced by the hypothalamus, stimulate the pituitary to secrete ACTH. In turn, ACTH triggers the release of cortisol from the adrenal gland. Cortisol has a direct negative feedback effect on the pituitary, and also on the hypothalamus, such that the secretion and synthesis of CRH, AVP and cortisol are inhibited.

A computer simulation of the hypothalamic-pituitary-adrenal axis, J. Gonzalez-Heydrich, R.J. Steingard and I Kohane, 1994, Eighteenth Annual Proceedings of the Symposium for Computer Applications in Medical Care, pp1010. (The Annual Symposium on Computer Applications in Medical Care currently does not have a website, but the text of this article can be found online here). PubMed ID: 7949852

Schematic diagram of the self-regulatory system for corticol secretion. CRH represents corticotropin-releasing hormone, and ACTH is adrenocorticotropic hormone.

Although this model is now more than 10 years old, it is still cited in the literature as one of the few mathematical models of the HPA axis which considers the dynamics of several hormones simultaneously, and doesn't focus solely on cortisol kinetics.