Adrenocorticotropic Hormone (ACTH)
A 39 amino acid peptide hormone produced by pituitary corticotroph cells that stimulates the adrenal cortex to produce cortisol. Corticotropin is the therapeutic form of ACTH, while cosyntropin (a synthetic ACTH fragment) is used diagnostically to test adrenal function.
Technical Context
ACTH (39 aa) is cleaved from POMC by prohormone convertase 1 in anterior pituitary corticotrophs. The N-terminal 24 amino acids contain the full biological activity — cosyntropin (ACTH 1-24, tetracosactide) retains complete adrenal-stimulating activity. ACTH binds MC2R on adrenal cortical cells, activating cAMP/PKA signalling to stimulate steroidogenesis (cortisol, aldosterone, adrenal androgens). ACTH secretion follows a circadian rhythm (peaking at 6-8 AM), is stimulated by CRH and vasopressin (synergistically), and is suppressed by cortisol (negative feedback). Corticotropin (therapeutic ACTH, repository formulation) is used for infantile spasms, multiple sclerosis flares, and other inflammatory conditions. Its mechanism involves both direct adrenal stimulation and extra-adrenal immunomodulatory effects through melanocortin receptors.