lACTH

lACTH is a term occasionally used in pharmacology and medical literature to refer to long-acting forms of adrenocorticotropic hormone (ACTH) or to modifications that extend ACTH’s in vivo half-life. There is no universally standardized molecule named lACTH, and most discussions focus on the native hormone ACTH (ACTH1-39) or on synthetic analogs designed to prolong activity. Consequently, articles about lACTH typically address either the natural peptide or long-acting ACTH formulations studied in research and clinical settings.

ACTH is produced by corticotroph cells in the anterior pituitary as part of the proopiomelanocortin (POMC) precursor. The active 39‑amino‑acid peptide ACTH1-39 stimulates the adrenal cortex, mainly the zona fasciculata, to synthesize and secrete glucocorticoids, particularly cortisol. ACTH release is driven by hypothalamic corticotropin-releasing hormone (CRH) and is subject to negative feedback by circulating cortisol.

Mechanism of action: ACTH binds to the melanocortin 2 receptor (MC2R) on adrenal cortical cells, activating Gs proteins and adenylate cyclase, increasing intracellular cAMP, and promoting the steroidogenic pathway, including cholesterol mobilization via the StAR protein. The net effect is increased cortisol production and release.

Clinical use: ACTH is employed in diagnostic testing, notably the ACTH stimulation test to assess adrenal reserve. Therapeutically, ACTH and its analogs have been used for certain inflammatory and autoimmune conditions, though long-term therapy is limited by adverse effects such as hypertension, edema, mood changes, and metabolic disturbances. Long-acting formulations aim to reduce dosing frequency but remain limited by safety, efficacy, and availability considerations.

See also: POMC, MC2R, Cosyntropin.