Modelling the hypothalamic-pituitaryadrenal (hpa) axis response to external perturbations with cortisol

Abstract

Glucocorticoids, the end products of the Hypothalamic-Pituitary-Adrenal (HPA) axis, are widely used as anti-inflammatory and immunosuppressive drugs. However, the feed-back effects of externally induced glucocorticoids on the HPA axis activity remain widely unknown. In this study, we use numerical simulations to investigate changes in the HPA axis activity caused by externally introduced cortisol. We emulate the basal HPA activity using a stoichiometric model of the HPA axis, and perturb its dynamics by abruptly changing cortisol levels during the course of numerical integration, thereby mimicking cortisol increase under treatment. Our study shows that the HPA axis activity is susceptible to perturbations by cortisol and that external cortisol pulses elicit different responses, depending on the dose and the time of cortisol introduction.