Identifying a Central Nervous System Perturbation that Explains Peripheral Hypocortisolism by Modeling the HPA Axis

The hypothalamus-pituitary-adrenal is the body ´s main stress management system, which responds to any threat to homeostasis or internal environmental balance of the body by controlling the body´s cortisol level. Dysregulation of the HPA axis is involved in numerous stress-related diseases including post-traumatic stress disorder and chronic fatigue syndrome. We present a new structured model that includes the glucocorticoid receptor that produces bistability in the HPA axis steady state. Small stresses do not perturb the system, but large stresses force the system to an alternate steady state. This bistable state can describe hypocortisolism, which is observed in these stress-related illnesses