Kinetic network modeling of theneuroendocrinehypothalamic-pituitary-adrenal axis dynamicswith particular attention on the role of alcoholas a digestif

Abstract

Kinetic network modeling of physiological processes offers unique possibility to better understand how complex responses emerge at the organism level through the integration of molecular reaction pathways. Here, we present our work on the development of a kinetic network model of the neuroendocrine hypothalamic-pituitary-adrenal (HPA) axis, describing the progression from a low-dimensional model with four species only to a more elaborate model that can emulate the net effect of cholesterol-rich food or alcohol (ethanol) intake on HPA axis dynamics. Importantly, our model can emulate cholesterol elimination from the global circulation by endogenous species such as highdensity lipoproteins (HDL) or by pharmacotherapy, for example, by statins, offering a unique possibility to examine using numerical simulations how adaptive transformations in HPA axis dynamics occur and providing insights into how our response to stress changes under acutely or chronically high/low cholesterol or acute/chronic exposure to alcohol (ethanol).