The HPA axis is one of the central entities in vegetative regulation. CRH is released from the paraventricular nucleus (PVN) of the hypothalamus (HT) and stimulates the secretion of ACTH from the pituitary. ACTH leads to cortisol release from the adrenal cortex. Cortisol acts on target tissues and gives negative feedback to the HT and the pituitary. The cortisol secretion oscillates in a circadian manner that is strongly influenced by the suprachiasmatic nucleus (SCN) of the HT. Existing mathematical models of the HPA axis are mostly based on a linear differential equation approach. In this models oscillatory behaviour is implemented by negative feedback. These models simulate the physiological phenomena quite well, but some pathophysiological relevant facts are not considered. Our approach combines the standard linear differential equation design with enzyme kinetics, e.g. Michaelis-Menten kinetics, and nonlinear mathematical expressions for (1.) circadian regulatory input from the SCN, (2.) half-life of ACTH and cortisol, and (3.) different types of corticoid receptors (GR and MR). In conclusion, our model not only simulates experimental data quite well but also takes physiological facts into consideration.

This work was supported by the EU through the Network of Excellence BioSim, Contract No. LSHB-CT-2004-005137.