What it is
Corticotropin-releasing hormone is a 41-amino-acid peptide made in the hypothalamus, the part of the brain that sits just above the pituitary. Its human sequence, from UniProt P06850, is:
SEEPPISLDLTFHLLREVLEMARAEQLAQQAHSNRKLMEII-NH2
It is cut from a 196-residue precursor (residues 154–194), and its last amino acid carries an amide cap. It goes by three names: CRH, CRF (corticotropin-releasing factor, the older term) and corticoliberin.
It is easy to mix up with the hormones it controls. It is not ACTH, which is the 39-residue pituitary hormone described in the ACTH entry, and it is not cortisol, which is a steroid, not a peptide at all.
What it does
UniProt's summary describes CRH as central to how the body adapts to stress. Released from the hypothalamus mainly in response to physical or psychological stress, it binds the receptor CRHR1, and to a lesser extent CRHR2, and sets off a three-step chain:
| Step | Messenger | Made in | Effect |
|---|---|---|---|
| 1 | CRH (41 amino acids) | Hypothalamus | Pituitary releases ACTH |
| 2 | ACTH (39 amino acids) | Pituitary | Adrenal glands release cortisol |
| 3 | Cortisol (steroid) | Adrenal cortex | Effects across the body; feeds back to damp steps 1 and 2 |
UniProt also lists the placenta as a source, and records an association from the literature that placental CRH acts as a "placental clock" that helps set the length of pregnancy and the timing of labour (citing PubMed 7585095). That is a description of the hormone's biology, not a use of it.
How it was found
The structure came from sheep. In 1981 Vale, Spiess, Rivier and Rivier described "a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin" (Science, 18 September 1981, PMID 6267699).
The sheep and human versions are not identical. Laying the sheep sequence printed on the Acthrel label beside UniProt's human sequence, they differ at 7 of 41 positions (2, 22, 23, 25, 38, 39 and 41) — our count from the two documents. The approved test drug is the sheep form.
The one approved product: a test, not a treatment
Acthrel (corticorelin ovine triflutate, Ferring) is a synthetic copy of sheep CRH. Its label gives a single job: helping to tell apart the two main causes of ACTH-dependent Cushing's syndrome once high cortisol has been established and an adrenal tumour ruled out.
| Item (Acthrel label) | Detail |
|---|---|
| Dose | 1 mcg/kg, intravenously over 30–60 seconds; the label says doses above 1 mcg/kg are not recommended |
| Samples | Two before the injection (15 minutes before and immediately before), then at 15, 30 and 60 minutes |
| Pituitary source (Cushing's disease) | ACTH and cortisol rise |
| Ectopic source (a tumour elsewhere making ACTH) | Little or no rise |
| Timing | Repeat tests at the same time of day, because morning and afternoon baselines differ |
The label's own figures for normal subjects show that difference: morning ACTH averaged 28 pg/mL at baseline and 68 at peak (143 subjects), afternoon 9 and 30 (70 subjects). The injected peptide clears in two phases, with half-lives of 11.6 minutes and 73 minutes.
The label's safety section is about dose. At 200 mcg given as a bolus, 4 of 60 volunteers and patients had falls in blood pressure, one had asystole requiring resuscitation, and three had brief "absence-like" loss of consciousness. It also advises against heparin to keep the cannula open, citing a possible interaction behind one severe drop in blood pressure. A result from this test is read by the endocrinologist who ordered it, alongside other tests.
Peptide or protein? The 41st residue
US regulation draws the line at 40. Under 21 CFR 600.3(h)(6), a protein is a defined amino-acid polymer "greater than 40 amino acids in size". CRH has 41, so in US law it is a protein, and Drugs@FDA lists Acthrel as BLA 020162 — a biologics licence number rather than a drug application. The general rule is set out in peptide vs protein; CRH is one of the few hormones that sits exactly on it.
The drug that blocks its receptor
A different approach reached the market in 2024. Crenessity (crinecerfont), approved on 2024-12-13 (Neurocrine, NDA 218808), is a small molecule, not a peptide. Its label describes it as a selective CRF type 1 receptor antagonist that blocks CRF binding in the pituitary, reduces ACTH and so lowers ACTH-driven adrenal androgens. It is approved as an add-on to glucocorticoid replacement in classic congenital adrenal hyperplasia, from age 4. It is evidence that the receptor is a drug target; it says nothing about CRH as a product.
Where it stands
- Human CRH: no approved product (Drugs@FDA returned no application with it as an active ingredient, 2026-10-06).
- Sheep CRH (Acthrel): approved since 1996-05-23, prescription, diagnostic only.
- Research record: PubMed indexes 6,533 records with the full name in the title or abstract, 128 tagged as randomised trials (2026-10-06). Searching the drug name "corticorelin" is not a usable count: PubMed maps it to CRH in general.
Related reading
The next step down the chain is in the ACTH entry, and the synthetic ACTH fragment used for a different adrenal test is in the cosyntropin entry. Another hypothalamic peptide that reaches the pituitary is vasopressin.