Cortisol synthesis and secretion

Cortisol is the main endogenous glucocorticoid, which affects a plethora of physiological functions, e.g., lipid and glucose metabolism, metabolic homeostasis and adaptation to stress. Cortisol production is primarily regulated by corticotropin (ACTH) in zona fasciculata. The stimulatory effect of ACTH on cortisol synthesis depends on cAMP dependent signaling, but also involves membrane depolarization and increased cytosolic Ca2+. Each of cAMP and Ca2+ induces the expression of StAR, stimulating intramitochondrial cholesterol transfer, as well as the steroidogenic enzymes in the pathway from cholesterol to cortisol (e.g., CHE, CYP17A1, CYP11B1).