Adrenocorticotropic Hormone (ACTH) is a 39-amino acid polypeptide hormone with a molecular weight of approximately 4540 Daltons. It is synthesized by corticotrope cells in the anterior pituitary gland in response to corticotropin-releasing hormone (CRH) from the hypothalamus. ACTH originates from the precursor molecule pre-pro-opiomelanocortin (pre-POMC), which is first translated into pro-opiomelanocortin (POMC), a 241-amino acid polypeptide. POMC is then processed through phosphorylation, glycosylation, and proteolytic cleavage into biologically active peptides, including ACTH.
ACTH plays a central role in the hypothalamic-pituitary-adrenal (HPA) axis, particularly in stress response. It stimulates the adrenal cortex—specifically the zona fasciculata—to secrete glucocorticoid hormones such as cortisol. These hormones are essential for regulating metabolism, immune response, and maintaining homeostasis during physiological stress. ACTH achieves this by binding to specific receptors (MC2R) on the surface of adrenocortical cells.
In clinical and research settings, measurement of ACTH levels is used to evaluate disorders of adrenal function, including Cushing’s syndrome, Addison’s disease, and secondary adrenal insufficiency. ACTH testing is also valuable in differentiating between adrenal and pituitary causes of cortisol imbalance and in assessing the integrity of the HPA axis during dynamic stimulation tests.
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