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The 41-residue stress hormone characterised in 1981 that sets the HPA axis in motion — and whose receptors, not the peptide, are what drug developers pursue.
Also known as: Corticotropin-releasing hormone · Corticotropin-releasing factor · CRF · Corticoliberin
Part of the Neuropeptides & signaling cluster
Overview
Corticotropin-releasing hormone (CRH, also CRF or corticoliberin) is the 41-amino-acid hypothalamic peptide that triggers ACTH and β-endorphin release from the pituitary and coordinates the body's autonomic, behavioural, cardiovascular, immune and endocrine responses to stress. It acts through two G-protein-coupled receptors, CRHR1 and CRHR2, which are investigational targets in psychiatry, heart failure and metabolic disease.
Source & context
Biological / chemical source: Hypothalamic paraventricular neurons and other brain regions (human, mouse, rat)
Primary research or clinical context: Endogenous hormone at the top of the hypothalamic-pituitary-adrenal axis; not a marketed medicine in the evidence reviewed — its receptors are investigational drug targets
What CRH is
“In 1981, Wylie Vale, Joachim Spiess, Catherine Rivier, and Jean Rivier reported on the characterization of a 41-amino-acid peptide from ovine hypothalamic extracts with high potency and intrinsic activity stimulating the secretion of adrenocorticotropic hormone and β-endorphin by cultured anterior pituitary cells. With its sequence known, this neuropeptide was determined to be a hormone and consequently named corticotropin-releasing hormone (CRH), although the term corticotropin-releasing factor (CRF) is still used” (Caruso et al., Biology 2022). The IUPHAR Guide to Pharmacology records it under the name corticotrophin-releasing hormone with human, mouse and rat entries; Wikipedia's article title, corticoliberin, is a third synonym. It is the top of the hypothalamic-pituitary-adrenal axis.
Physiology: the stress axis
CRH and related peptides — the urocortins, sauvagine and urotensin — “play a central role in the co-ordination of autonomic, behavioural, cardiovascular, immune and endocrine responses to stressful stimuli” (Hillhouse et al., Biochemical Society Transactions 2002). Released from the hypothalamus, CRH drives pituitary ACTH, which drives adrenal cortisol; the axis “is central to homeostasis, stress responses, energy metabolism, and neuropsychiatric function” (Miller, Hormone Research in Paediatrics 2018). A CRH-binding protein modulates its availability across species from invertebrates to humans (Ketchesin et al., Stress 2017). Cosyntropin, the ACTH fragment profiled separately, is the diagnostic peptide one step downstream.
Receptors
CRH's actions “are mediated through activation of two types of G-protein-coupled receptors encoded by separate genes” (Hillhouse et al. 2002). “CRHR1 is predominantly expressed in the brain and plays a vital role in the hypothalamic-pituitary-adrenal (HPA) axis stress responses,” while CRHR2 has distinct roles including in the cardiovascular system (Takefuji and Murohara, Circulation Journal 2019). Urocortin, profiled on this site, is the family member with higher affinity for CRHR2. This receptor split is why the same peptide family is studied in anxiety and depression on one hand and heart failure on the other — the ClinicalTrials.gov snapshot for September 2026 includes a suspended phase 2 trial of a CRF2 agonist in worsening heart failure.
| Receptor | Main expression | Studied in |
|---|---|---|
| CRHR1 | Brain | HPA-axis stress responses; psychiatry |
| CRHR2 | Brain and cardiovascular system | Cardiovascular function; heart failure (CRF2 agonist trial) |
Beyond the pituitary: brain circuits, sleep and obesity
Recent neuroscience has traced CRH signalling in specific circuits. CRH signalling from the prefrontal cortex to the lateral septum suppresses interaction with familiar mice (de León Reyes et al., Cell 2023); CRH modulates NREM sleep consolidation through the thalamic reticular nucleus (Cumpana et al., Nature Communications 2025); and nucleus accumbens CRH neurons projecting to the bed nucleus of the stria terminalis promote wakefulness and positive affect (Pan et al., Neuroscience Bulletin 2024). A 2024 review connects CRH to obesity “from fetal life to adulthood” (Vasconcelos et al., Obesity Reviews 2024). These are mechanistic studies in animals; they define where a CRH-targeted drug might act, not what it would do in a person.
Relation to other peptides on this site
CRH sits with GHRH, GnRH (gonadorelin) and TRH (protirelin) as a hypothalamic releasing hormone, each commanding a pituitary axis. Its family member urocortin and its downstream product cosyntropin (ACTH 1-24) both have profiles. The β-endorphin it co-releases is profiled among the opioid peptides. Together these pages map the endocrine chain from hypothalamic signal to adrenal output.
Regulatory status
CRH is an endogenous hormone and a laboratory reagent. The evidence pack contains no marketing authorisation for a CRH product, so none is claimed here; the therapeutic interest documented in the pack is in receptor agonists and antagonists, which are investigational. ClinicalTrials.gov listed 42 registered studies naming CRH at the September 2026 snapshot, largely as a measured hormone or a receptor target. This profile is educational and is not guidance on obtaining or using any product.
Structure & chemistry
Molecular identity & reference confidence
Source-supported reference
Reference values are taken from the cited molecular record or curated profile. A database match is not independent laboratory verification; modifications, counter-ions, and formulations can change the measured mass.
- Molecular form
- 41-residue amidated peptide, first characterised from ovine hypothalamic extracts in 1981
- Species
- Not established by this molecular identity audit
- Termini (N / C)
- Not specified / Amide
Average reference mass
Reference policy updated: 2026-10-05
- IUPHAR/BPS source snapshot · 2026-10-01
- PubChem molecular record · 2026-10-01
- Molecular formula
- C208H344N60O63S2
- Average reference mass
- ≈ 4,757
- Receptors
- CRH receptor 1 (CRHR1, predominantly brain) and CRH receptor 2 (CRHR2) — class B G-protein-coupled receptors shared with the urocortins
- Backbone
- 41-residue amidated peptide, first characterised from ovine hypothalamic extracts in 1981
- C-terminus
- Amide
- Status
- Endogenous hormone; receptors are investigational drug targets; no CRH product approval appears in the evidence reviewed as of September 2026
- PubChem CID: 16186200
- IUPHAR ligand: 912
- CAS RN: 9015-71-8
- UNII: 305OE8862Y
Chemistry values: curated profile, PubChem, IUPHAR/BPS Guide to Pharmacology · fetched 2026-10-01.
Clinical development snapshot
ClinicalTrials.gov lists 85 registered studies with “CRH” as an intervention (snapshot 2026-10-01). A registry footprint is not evidence of efficacy or approval.
| NCT | Title | Phase | Status | Updated |
|---|---|---|---|---|
| NCT06763341 | A Phase 1 Study of AOH1996 in Patients With Relapsed/Refractory Acute Myeloid Leukemia | Phase 1 | recruiting | 2026-09-29 |
| NCT00001721 | Study of Smith-Lemli-Opitz Syndrome | — | completed | 2026-09-28 |
| NCT05564390 | MYELOMATCH: A Screening Study to Assign People With Myeloid Cancer to a Treatment Study or Standard of Care Tr | Phase 2 | recruiting | 2026-09-25 |
| NCT06577441 | Testing the Addition of an IDH2 Inhibitor, Enasidenib, to Usual Treatment (Cedazuridine-Decitabine) for Higher | Phase 2 | recruiting | 2026-09-22 |
| NCT06317649 | Venetoclax and HMA Treatment of Older and Unfit Adults With FLT3 Mutated Acute Myeloid Leukemia (AML) (A Myelo | Phase 2 | recruiting | 2026-09-22 |
| NCT07153497 | Testing the Use of an IDH1 Inhibitor, Olutasidenib, in Acute Myeloid Leukemia Added to ASTX727 and Venetoclax; | Phase 2 | not yet recruiting | 2026-09-09 |
CRH (corticorelin) — reconstitution calculator
Enter how much peptide is in the vial and how much diluent (e.g. bacteriostatic water) is added. The tool returns the resulting solution concentration — and, for any amount you type, the volume it corresponds to. This is educational arithmetic, not a dosing recommendation.
Reference form: 41-residue amidated peptide, first characterised from ovine hypothalamic extracts in 1981Average reference mass: 4,757 Da
Enter an amount to see the volume it corresponds to.
Educational concentration mathematics only. This tool does not recommend a dose, amount, or protocol, and nothing here is medical advice. Many peptides are not authorized by Health Canada for human use — see our reconstitution and bacteriostatic-water guides for context.
Change log
Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.
- IdentifiersCross-linked to IUPHAR ligand 912 and PubChem CID 16186200.
- TrialsClinicalTrials.gov snapshot added: 85 registered studies, highest phase 4.
- EditorialProfile content reviewed and updated by the editorial team.
FAQ about CRH (corticorelin)
What is CRH (corticorelin)?+
Corticotropin-releasing hormone (CRH, also CRF or corticoliberin) is the 41-amino-acid hypothalamic peptide that triggers ACTH and β-endorphin release from the pituitary and coordinates the body's autonomic, behavioural, cardiovascular, immune and endocrine responses to stress. It acts through two G-protein-coupled receptors, CRHR1 and CRHR2, which are investigational targets in psychiatry, heart failure and metabolic disease.
What Canadian product status is recorded for CRH (corticorelin)?+
Canadian product status for CRH (corticorelin) has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.
What is the typical length of CRH (corticorelin)?+
CRH (corticorelin) is commonly described as approximately 41 amino acids (Hypothalamic releasing hormone).
What is CRH?+
Corticotropin-releasing hormone, a 41-amino-acid hypothalamic peptide that stimulates ACTH and β-endorphin release from the pituitary and coordinates the body's stress responses. It is also called CRF or corticoliberin.
What does CRH do?+
It starts the HPA axis: CRH drives pituitary ACTH, which drives adrenal cortisol, and it coordinates autonomic, behavioural, cardiovascular and immune responses to stress.
What receptors does CRH act on?+
CRHR1, mainly in the brain and central to stress responses, and CRHR2, which also has cardiovascular roles. Both are shared with the urocortins.
Is CRH a drug?+
No CRH product approval appears in the evidence reviewed. Drug development targets its receptors — for example a CRF2 agonist trial in heart failure.
How is CRH related to cosyntropin?+
CRH is one step upstream: it releases ACTH, and cosyntropin is the synthetic 1–24 fragment of ACTH used as a diagnostic.
Related peptides
References & further reading
- 1.Caruso et al. (2022). Corticotropin-Releasing Hormone: Biology and Therapeutic Opportunities. Biology (Basel)
- 2.Hillhouse et al. (2002). Corticotropin-releasing hormone receptors. Biochemical Society Transactions
- 3.Takefuji & Murohara (2019). Corticotropin-Releasing Hormone Family and Their Receptors in the Cardiovascular System. Circulation Journal
- 4.Miller (2018). The Hypothalamic-Pituitary-Adrenal Axis: A Brief History. Hormone Research in Paediatrics
- 5.de León Reyes et al. (2023). Corticotropin-releasing hormone signaling from prefrontal cortex to lateral septum suppresses interaction with familiar mice. Cell
- 6.Cumpana et al. (2025). Corticotropin-releasing hormone modulates NREM sleep consolidation through the thalamic reticular nucleus. Nature Communications
- 7.Vasconcelos et al. (2024). Corticotropin-releasing hormone and obesity: From fetal life to adulthood. Obesity Reviews
- 8.Taylor & Fishman (1988). Corticotropin-releasing hormone. New England Journal of Medicine