Author: Marcus Belke, Institute of Physiology, University of Marburg.
Names and affiliation of other authors:
Bastian T Wollweber, Karlheinz Voigt, Hans A Braun
Institute of Physiology, University of Marburg
Oral or poster: Poster
Increased levels of the “stress” hormone cortisol which indicate disturbances of the hypothalamo-pituitary-adrenal (HPA) axis belong to the most significant biological markers of mental depression. The HPA axis controls the release of cortisol in the following way: The paraventricular nucleus (PVN) of the hypothalamus (H) releases CRH which stimulates the secretion of ACTH from the pituitary (P). ACTH leads to cortisol release from the adrenal cortex (A). Cortisol acts on target tissues and gives negative feedback to the hypothalamus and the pituitary. The cortisol level shows a clear circadian rhythm with a significant peak in morning hours. In depressive patients the cortisol level is permanently increased which partly also destroys the circadian rhythm.
We have developed a mechanism based computer model of the HPA axis for the examination of the biological rhythms and their disturbances. 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 suprachiasmatic nucleus SCN, (2.) half-life of ACTH and cortisol, and (3.) different types of corticoid receptors (GR and MR). As crucial parameters for the generation and shape of the rhythmic cortisol release, we identified a combination of nonlinear positive and negative feedback loops according to the antagonistic action of cortisol on the GR and MR receptors.