A schematic representation of the hypothalamic-pituitary-adrenocortical (HPA) system. Cortisol acts on the brain through binding to glucocorticoid receptors (GRs). Binding to these receptors in some regions of the brain, including the hippocampus, cingulate, and frontal cortex triggers a negative feedback system that dampens release of corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH), thus modulating HPA activity