hormonesACTH

Adrenocorticotropic hormone (ACTH) is a peptide hormone produced by corticotroph cells of the anterior pituitary gland. It is derived from the larger precursor protein proopiomelanocortin (POMC) and consists of 39 amino acids in humans. ACTH acts primarily to stimulate the adrenal cortex to produce glucocorticoids, mainly cortisol, and to a lesser extent androgens.

ACTH secretion is regulated by hypothalamic signals, primarily corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP). Its release shows a pulsatile, diurnal rhythm with peak levels in the early morning. Cortisol exerts negative feedback on both the pituitary and hypothalamus, helping to regulate ACTH production.

In the adrenal cortex, ACTH binds to the melanocortin 2 receptor (MC2R) onZona fasciculata and reticularis cells. This Gs-protein–coupled receptor activates adenylate cyclase and increases cyclic AMP, stimulating steroidogenic enzymes and cholesterol mobilization, leading to increased synthesis and secretion of cortisol and, to a lesser extent, adrenal androgens.

Physiologically, cortisol helps regulate metabolism, the stress response, immune function, and inflammation, and maintains cardiovascular homeostasis. In clinical context, excessive ACTH production can cause Cushing disease (pituitary source) or ectopic ACTH syndrome, while deficient ACTH leads to secondary adrenal insufficiency. The ACTH stimulation test assesses adrenal gland function by measuring cortisol response to synthetic ACTH (cosyntropin). ACTH also reflects POMC-derived peptide processing, including other peptides such as MSH and beta-endorphin.