Adrenocorticotropic

Adrenocorticotropic hormone, commonly abbreviated ACTH and also known as corticotropin, is a peptide hormone produced by the corticotroph cells of the anterior pituitary gland. It is derived from the pro-opiomelanocortin (POMC) precursor. The release of ACTH is stimulated by corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) from the hypothalamus, and its secretion exhibits a circadian rhythm with peaks in the early morning. ACTH production is regulated by negative feedback from cortisol and, to a lesser extent, other glucocorticoids.

ACTH acts primarily on the melanocortin type 2 receptor (MC2R) located on the adrenal cortex, especially the zona fasciculata and zona reticularis. Binding to MC2R activates the Gs protein–cAMP signaling pathway, leading to increased expression of steroidogenic enzymes and the transport of cholesterol into mitochondria via the Steroidogenic Acute Regulatory (StAR) protein. This cascade culminates in the synthesis and secretion of glucocorticoids (cortisol and, to a smaller extent, corticosterone) and adrenal androgens, and it also promotes adrenal cortical growth. Cortisol exerts negative feedback on both the hypothalamus and pituitary to limit ACTH production.

Clinically, ACTH dynamics help diagnose adrenal disorders. The ACTH stimulation test, using synthetic ACTH (cosyntropin) or ACTH1-24, assesses adrenal reserve by measuring cortisol response. Low cortisol with inappropriately low ACTH points to secondary adrenal insufficiency, whereas high ACTH with elevated cortisol suggests Cushing disease or ectopic ACTH production. ACTH is a 39-amino-acid peptide derived from POMC and has historically been used therapeutically in various settings, though use varies with current practice.