ACTH

Adrenocorticotropic hormone (ACTH), also known as corticotropin, is a peptide hormone produced by the anterior pituitary gland’s corticotroph cells. It is synthesized from the larger precursor molecule proopiomelanocortin (POMC) and is released in a pulsatile, circadian pattern, with higher levels in the early morning.

ACTH acts primarily on the adrenal cortex, stimulating the zona fasciculata and reticularis to synthesize and secrete glucocorticoids, especially cortisol, and androgens. It also has a trophic effect, promoting growth and maintenance of the adrenal cortex. The biological action of ACTH is mediated by the melanocortin 2 receptor (MC2R) on adrenal cortex cells; signaling requires the accessory protein MRAP for proper receptor trafficking and function.

Regulation of ACTH secretion is dominated by corticotropin-releasing hormone (CRH) from the hypothalamus, with vasopressin and other factors modulating release. Cortisol and related glucocorticoids provide negative feedback to reduce CRH and ACTH production. Physiological stress, illness, fever, and hypoglycemia can increase ACTH release.

Clinical significance includes disorders of the hypothalamic-pituitary-adrenal axis. Elevated ACTH with hypercortisolism suggests Cushing disease or ectopic ACTH production. Low or inappropriately normal ACTH with low cortisol indicates secondary or tertiary adrenal insufficiency, while elevated ACTH with low cortisol characterizes primary adrenal insufficiency (Addison’s disease). An ACTH stimulation test uses synthetic cosyntropin (ACTH analog) to assess adrenal function. Synthetic ACTH is used diagnostically and, in limited therapeutic contexts, for treatment of certain conditions.