ACTH (1-39)

At a Glance

Classification: Endogenous 39-amino-acid pituitary peptide hormone derived from pro-opiomelanocortin (POMC); melanocortin-2 receptor (MC2R) agonist with activity at other melanocortin receptors; adrenal steroidogenesis stimulator

ACTH (1-39) is the full-length adrenocorticotropic hormone made by the anterior pituitary. Its main job is to tell the adrenal cortex to make cortisol. It is a real, long-studied hormone with genuine prescription-drug history. Repository corticotropin injection (Acthar Gel) was first approved by the FDA in 1952 and is labeled for conditions including infantile spasms and acute exacerbations of multiple sclerosis. Acthar Gel contains porcine-derived ACTH in a slow-release gel. Purified Cortrophin Gel is another FDA-approved repository corticotropin product. It has been studied for: - Infantile spasms - Acute multiple sclerosis relapses - Nephrotic syndrome, rheumatologic, and other inflammatory conditions - Diagnostic testing of adrenal function (mostly with the shorter synthetic fragment ACTH 1-24, cosyntropin). Synthetic "ACTH 1-39" sold as a research chemical is not the same thing as an approved, quality-controlled corticotropin product.

What Is ACTH (1-39)?

ACTH is cut from a larger precursor protein, pro-opiomelanocortin (POMC), which also gives rise to α-MSH and β-endorphin. ACTH (1-39) → full-length native hormone, 39 residues ACTH (1-24), cosyntropin / tetracosactide → synthetic N-terminal fragment that carries the adrenal-stimulating activity; used mainly for the ACTH stimulation test Repository corticotropin (Acthar Gel) → naturally sourced, porcine-derived mixture of ACTH analogs and other pituitary peptides in a long-acting gel These are related but not interchangeable products.

What Are Researchers Studying?

How Does It Work?

ACTH (1-39) ↓ melanocortin-2 receptor (MC2R, with its accessory protein MRAP) on adrenal cortex cells ↓ cAMP signaling ↓ increased synthesis and release of cortisol (and other adrenal steroids) ↓ glucocorticoid anti-inflammatory and metabolic effects. ACTH can also activate other melanocortin receptors, which may contribute non-adrenal effects. The receptor family was cloned in 1992.

What Does the Research Show?

Notable Studies

What We Still Don't Know

- Which clinical effects of repository corticotropin come from non-adrenal melanocortin receptor activity rather than cortisol - Comparative effectiveness versus modern corticosteroid regimens for many labeled inflammatory indications - Optimal regimens for infantile spasms relative to prednisolone and vigabatrin (trial results vary) - Quality, purity, and stability of research-market synthetic ACTH 1-39, which is not an approved product - Any benefit in healthy people; none has been established

Related Compounds

Sources & References

1. Baram TZ et al. High-dose corticotropin (ACTH) versus prednisone for infantile spasms: a prospective, randomized, blinded study. Pediatrics. 1996.
2. Rose AS et al. Cooperative study in the evaluation of therapy in multiple sclerosis. ACTH vs. placebo--final report. Neurology. 1970.
3. Thompson AJ et al. Relative efficacy of intravenous methylprednisolone and ACTH in the treatment of acute relapse in MS. Neurology. 1989.
4. Poola N et al. Pharmacokinetics and Pharmacodynamics of Repository Corticotropin Injection Compared With Synthetic ACTH1-24 Depot and Methylprednisolone in Healthy Subjects. Clinical Pharmacology in Drug Development. 2022.
5. Mountjoy KG, et al. The cloning of a family of genes that encode the melanocortin receptors. Science. 1992.
6. Kaplan J, et al. Acthar Gel Treatment for Patients with Autoimmune and Inflammatory Diseases: An Historical Perspective and Characterization of Clinical Evidence. Clin Drug Investig. 2023.