Adrenocorticotropic hormone (ACTH, corticotropin) is a 39-residue peptide cleaved from pro-opiomelanocortin (POMC) and released by corticotroph cells of the anterior pituitary. Its receptor, the melanocortin-2 receptor (MC2R), is the only melanocortin receptor selective for ACTH, and it is expressed almost exclusively in the adrenal cortex.
Tetracosactide is the synthetic N-terminal 24-residue fragment of ACTH — ACTH(1-24). It is the shortest fragment that retains full corticotropic activity, and it is one of a small number of peptides that hold a UK marketing authorisation. This explainer sets out the axis, the receptor pharmacology, and the UK regulatory position.
The corticotropin axis
Hypothalamic corticotropin-releasing hormone (CRH) drives pituitary ACTH release; ACTH drives adrenal cortisol synthesis; cortisol feeds back negatively on both the hypothalamus and the pituitary. The axis is a closed loop, and the diagnostic question in suspected adrenal insufficiency is where in that loop the failure sits — adrenal (primary), pituitary (secondary) or hypothalamic (tertiary).
The ACTH stimulation test interrogates the adrenal end directly: an exogenous ACTH fragment is administered and the cortisol response measured. A blunted response points to a failing adrenal cortex; a preserved response points upstream.
MC2R, MRAP and receptor selectivity
ACTH signalling at MC2R depends on an accessory protein, MRAP (melanocortin-2 receptor accessory protein). Without MRAP, MC2R is poorly trafficked to the cell surface and poorly responsive. The genes for the five melanocortin receptors were cloned in 1992; MC2R's dependence on MRAP was established later, and loss-of-function variants in MC2R or MRAP underlie familial glucocorticoid deficiency, a rare monogenic form of ACTH resistance.
This is the distinction that matters when reading the wider melanocortin literature. MC1R, MC3R, MC4R and MC5R ligands — afamelanotide, melanotan II, bremelanotide, setmelanotide — act at receptors with little to do with the adrenal axis. An ACTH fragment is defined by MC2R selectivity.
What tetracosactide is
Tetracosactide is ACTH(1-24), the first 24 residues of the natural hormone. Residues 25-39 are not required for corticotropic activity, and the 1-24 sequence is conserved across mammalian species — which is why the synthetic fragment is not species-specific. In the United States the same molecule is named cosyntropin.
The UK label for tetracosactide provides for both diagnostic and therapeutic use; some other jurisdictions restrict the product to diagnosis. That is a licensing difference, not a pharmacological one.
UK licensing
Tetracosactide acetate is licensed in the UK as a prescription-only medicine (POM) under the Human Medicines Regulations 2012, within the framework set by the Medicines Act 1968. The marketing authorisation is held by Atnahs Pharma UK Ltd, and the electronic Medicines Compendium lists two presentations: an immediate-release solution and a zinc-phosphate depot suspension.
The two are not interchangeable in intent. The immediate-release solution is used for the short ACTH stimulation test; the depot suspension is designed for a prolonged steroidogenic effect, and was traditionally used where a longer ACTH action was wanted.
Because tetracosactide is a licensed POM, it sits on the other side of the medicines boundary from the research-peptide market. A product sold for laboratory use is not covered by this authorisation, and any product supplied for human use under a medicinal claim is an unlicensed medicine unless it holds its own authorisation. The MHRA assesses that boundary case by case, and states that it disregards "research purposes" labelling where that label is used to avoid medicines regulation.
Where the evidence sits
The diagnostic application is well established and, in our grading scheme, sits at Strong: the ACTH stimulation test is standard practice in the investigation of suspected adrenal insufficiency, and its performance characteristics have been the subject of large comparative studies.
The therapeutic use of depot ACTH preparations is graded lower. It was historically used as an alternative to systemic corticosteroids in a number of inflammatory and autoimmune conditions, and it has narrowed as other options became available.
Evidence for ACTH fragments outside these licensed uses is thin. There is no substantial modern trial literature for ACTH(1-24) in the recreational or performance context in which the melanocortin analogues are more usually discussed.
The research-use-only line
Nothing in this article is a use recommendation. Tetracosactide is a prescription-only medicine; it is not supplied as a self-administered research compound and it has no place in a personal protocol. Where an unlicensed ACTH-fragment product is offered with a "research use only" label but is evidently intended for human use, the MHRA's stated position is that it disregards that label — the test is the product's intended purpose, not the words on the vial.
Research interest in this axis is legitimate and active: MC2R/MRAP pharmacology, ACTH resistance syndromes, and the use of ACTH fragments as tools to probe adrenal steroidogenesis. That research runs under trial authorisation and institutional oversight, not through grey-market supply.
This article is AI-researched and editorially reviewed. It is provided for research and educational purposes only and is not medical advice. Research peptides are not licensed for human consumption in the UK.