Cortisol is a steroid hormone belonging to the corticosteroid class known as glucocorticoids. It is produced and secreted by the adrenal gland and is involved in a variety of functions including the stress response, immune response, inflammation and carbohydrate metabolism. Cortisol is also available as a pharmaceutical therapeutic known as hydrocortisone.  This paper provides an overview of cortisol, its involvement in disease and its use as a therapeutic.

Although cortisol is involved in a variety of functions, it is best known as the stress hormone. So it is not surprising that cortisol production is induced by stressors that activate the hypothalamic-pituitary-adrenal (HPA) axis—a system of interactions and feedback loops between three major glands that secrete hormones into the bloodstream.

Following stress, the hypothalamus secretes corticotropin-releasing hormone (CRH). CRH then stimulates CRH receptors (CRHRs) in the pituitary gland to produce another hormone called adrenocorticotropin, or ACTH. Some stressors, such as hypoglycemia, hemorrhage and immune stimuli, can trigger the release of vasopressin—another hypothalamic substance that promotes ACTH production. ACTH then stimulates the adrenal cortex to produce cortisol. Other factors such as cytokines and fat cells can also stimulate the HPA at any level.

The produced cortisol is bound to corticosteroid-binding globulin (CBG) or cortisol-binding protein (CBP), which transports it through circulation to different tissues. There, cortisol activity is regulated by enzymes called 11β-hydroxysteroid dehydrogenase. Active cortisol binds to mineralocorticoid and glucocorticoid receptors (MRs and GRs) in the tissue to form a complex that is transported into the nucleus of cells where it modulates expression of genes sensitive to cortisol.