Cortisol (hydrocortisone, compound F) is the most potent glucocorticoid produced by the human adrenal complex. As with most other adrenal steroids, cortisol is synthesized from cholesterol by the adrenal cortex via a series of enzymatic-mediation steps. The first and rate-limiting step in adrenal steroidogenesis is conversion of cholesterol to pregnenolone. Step one is stimulated by pituitary adrenocorticotropic hormone (ACTH) which is, in turn, regulated by the hypothalamic corticotrophin-releasing factor (CRF). ACTH and CRF secretion are inhibited by high levels of cortisol. In plasma, most cortisol is bound with high affinity to corticosteroid-binding globulin (CBG, transcortin), with much of the remainder loosely bound to albumin. Physiologically effective in anti-inflammatory activity and blood pressure maintenance, cortisol is involved in gloconeogenesis. Cortisol acts through specific intracellular receptors and affects numerous other physiologic systems including: immune function, glucose-counter regulation, vascular tone, substrate utilization and bone metabolism. Cortisol is excreted primarily in urine and in an unbound (free) form.