Adrenocorticotropic hormone (ACTH) receptor (ACTH receptor)

The adrenocorticotropic hormone release pathway describes the neuroendocrine signaling cascade that regulates stress adaptation through glucocorticoid secretion. In response to stressors, corticotropin-releasing hormone (CRH) is secreted by hypothalamic neurons; CRH then stimulates anterior pituitary corticotrophs to secrete adrenocorticotropic hormone (ACTH). Circulating ACTH binds specifically to its G protein-coupled melanocortin 2 receptors on cells in the zona fasciculata of the adrenal cortex. This triggers intracellular cAMP signaling pathways that upregulate cholesterol transport and activate key steroidogenic enzymes—ultimately increasing synthesis and release of cortisol into circulation. Cortisol exerts negative feedback at both hypothalamic and pituitary levels, tightly regulating further activation within this system[1][4]. Dysregulation can result in various endocrine diseases including Cushing’s syndrome/disease when overactive or Addison’s disease when underactive.

Other names

Melanocortin 2 receptorMC2RACTH-RAdrenocorticotropin receptor

Drugs like cosyntropin mimic endogenous ACTH by binding to and activating the adrenocorticotropic hormone receptor on adrenal cortex cells. This stimulates cAMP production and activates steroidogenic enzymes leading to increased cortisol synthesis and secretion[1].