Figure 2. Endogenous circadian rhythm of cortisol.

Cortisol, the primary glucocorticoid in humans, is produced by the adrenal glands and is regulated by one of the major neuroendocrine systems, namely, the hypothalamic-pituitary-adrenal (HPA) axis. Typical physiological cortisol concentrations function to regulate energy mobilization in the body and thus follows a circadian rhythm in which changes in circulating cortisol generally precede daily activity patterns; cortisol values rise sharply just prior to the onset of activity (prewaking) and then gradually decline across the day to reach nadir at the end of the active period (onset of sleep) (based on [74]). The HPA axis also functions to integrate physiological systems (e.g., immune, cardiovascular, reproductive, metabolism, central nervous system) to rapidly adapt to changes in the environment. Strong bidirectional feedback between the HPA axis and these systems place it as the fulcrum of typical physiology; thus, HPA axis dysregulation is implicated in many medical conditions.