Melanocortin receptor type 2 (MC2R)

Melanocortin receptor type 2 (MC2R), also known as the adrenocorticotropic hormone (ACTH) receptor, is a G protein-coupled receptor predominantly expressed in the adrenal cortex, where it is essential for mediating adrenocorticotropic hormone (ACTH)-stimulated glucocorticoid (cortisol) synthesis. This receptor uniquely requires the melanocortin 2 receptor accessory protein (MRAP) for proper folding, trafficking to the plasma membrane, and functional response to ACTH. Upon ACTH binding, MC2R activates the Gαs protein, which in turn stimulates adenylyl cyclase to increase intracellular cAMP, ultimately regulating steroidogenic enzyme expression and promoting corticosteroid production. Mutations or disruptions in MC2R or MRAP cause rare forms of familial glucocorticoid deficiency, characterized by ACTH resistance and adrenal insufficiency[1][4][7][8]. MC2R is an established therapeutic and diagnostic target, with synthetic ACTH analogues used in adrenal function testing and rare antagonists under investigation[4][8].

Other names

Adrenocorticotropic hormone receptorACTH receptorMC2 receptor

Stimulation: ACTH agonists bind MC2R and activate adenylyl cyclase via Gαs, increasing cAMP and promoting glucocorticoid (cortisol) synthesis in the adrenal cortex[4][1][7][8]. Antagonism: Inhibitors block ACTH binding and subsequent signal transduction.