Urocortin

Ucn1, Ucn2 (urocortin II, also called stresscopin-related peptide), Ucn3 (urocortin III, also called stresscopin); members of the corticotropin-releasing factor (CRF/CRH) family

Cardiovascular & circulation

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Summary

Class: Naturally occurring peptides of the CRF family — urocortin 1 is 40 amino acids, urocortins 2 and 3 are 38–43 amino acid peptides with different receptor selectivity
Mechanism: Urocortin 1 activates both CRF receptors (CRF-R1 and R2); urocortins 2 and 3 act selectively at CRF-R2, which in the heart and vessels means vasodilation and increased contractility rather than a stress response
Routes studied: Intravenous infusion and bolus in human physiology and small cardiovascular studies; no chronic human dosing
Half-life: Short; minutes to tens of minutes depending on the peptide and assay
Storage: Research peptides; lyophilised, cold storage. Not consumer products
Regulatory status: Not approved anywhere, in any form

Doses are as reported in studies or by the community — never recommendations.

1What it is

The urocortins are your own peptides, and they sit in the same family as CRF — the hypothalamic hormone that starts the stress cascade ending in cortisol. Urocortin 1 was identified in 1995 and named after urotensin, a related fish peptide. Urocortins 2 and 3 followed around 2001.

The family splits usefully by receptor. CRF-R1 is the stress receptor: activating it drives ACTH, cortisol and anxiety-like behaviour. CRF-R2 is found in the heart, blood vessels, skeletal muscle and parts of the brain, and activating it produces something quite different — vasodilation, stronger cardiac contraction, better renal perfusion. Urocortin 1 hits both. Urocortins 2 and 3 are CRF-R2-selective, which is why urocortin 2 in particular was taken into human cardiovascular studies: it offers inotropic and vasodilator effects without the stress-axis activation.

These are laboratory and clinical-research peptides with no self-directed use. Community use: essentially none documented.

2How it's thought to work

CRF-R2 in the cardiovascular system. raises cAMP in cardiomyocytes and vascular smooth muscle, increasing contractility and causing dilation; increases cardiac output while lowering systemic vascular resistance.

Kidney. increases renal blood flow and sodium excretion, and suppresses aldosterone and renin in human heart-failure studies — an unusual and desirable combination in heart failure.

CRF-R1 (urocortin 1 only). drives ACTH and cortisol release and anxiety-like and anorectic effects in animals; also mediates urocortin 1's potent appetite suppression.

Skeletal muscle. CRF-R2 activation by urocortin 2 opposes atrophy and improves glucose uptake in rodent models.

Pancreas. urocortin 3 is co-secreted with insulin from beta cells and acts locally on islet signalling — a distinct physiological role from the cardiovascular one.

Urocortin at the CRF2 receptor — the stress-peptide receptor found on the heart rather than the pituitary. Coronary vessels widen and contractility rises, separately from the HPA axis that urocortin's relative CRH drives.Schematic — not to scale

3What the research shows

Urocortin 2 in heart failure

The most developed human work. Intravenous urocortin 2 in patients with stable systolic heart failure increased cardiac output, lowered systemic vascular resistance, increased left ventricular ejection fraction acutely, increased renal blood flow and suppressed renin, aldosterone and natriuretic peptides, without raising heart rate much (Davis 2007, J Am Coll Cardiol; Chan and colleagues, subsequent studies from the Christchurch, New Zealand group). Small, short, mechanistic — but consistent. [4]

Urocortin 2 in healthy volunteers

Infusion produces flushing, a fall in blood pressure, a rise in cardiac output, and dose-dependent increases in ACTH and cortisol that are smaller than with CRF or urocortin 1 (Davis and colleagues; Venkatasubramanian 2013, Circulation/related for vascular effects †).

Clinical development for acute heart failure

Urocortin 2 analogues were advanced into early clinical development for acute heart failure in the 2010s. No programme has produced a positive Phase 3, and the field's enthusiasm for acute inotrope-vasodilators cooled considerably after serelaxin (#154) and nesiritide. Current programme status should be checked against registries †.

Graded C/B

Urocortin 1

Human data are sparse. In animals it is a powerful appetite suppressant and anxiogenic agent via CRF-R1, and it is studied in stress, addiction and depression models. It is also expressed in Edinger-Westphal nucleus neurons implicated in stress adaptation. Its dual-receptor action makes it less attractive therapeutically than urocortin 2.

Urocortin 3 and islet biology

Rodent and human-islet work shows urocortin 3 is stored in beta cells and co-released with insulin, acting on delta cells to shape the islet's own feedback. Relevant to diabetes biology; no human intervention data.

Graded A (negative, by proxy)

Stress, anxiety and the CRF-R1 antagonist story

The therapeutic effort on the stress side of this family went into CRF-R1 antagonists for depression and anxiety. Multiple compounds (for example verucerfont, pexacerfont) failed to show benefit in randomised trials, which is a sobering result for the whole CRF-pathway-in-mood hypothesis.

4Reported side effects and interactions

Literature-reported

In human infusions, flushing, a drop in blood pressure, headache and a sensation of warmth are the common effects; higher doses of urocortin 1 or CRF produce measurable ACTH and cortisol rises and subjective anxiety. No long-term human safety data for any urocortin.

Community-reported

None. Not in self-directed use.

Theoretical. Stimulating cardiac contractility pharmacologically has a poor long-term track record in heart failure; the acute haemodynamic profile should not be read as a chronic benefit. CRF-R1 activation (urocortin 1) would be expected to raise cortisol and provoke anxiety, which is a mechanism argument against any informal use.

Interactions. Additive hypotension with vasodilators and antihypertensives. Anything affecting the HPA axis interacts conceptually with urocortin 1. No formal interaction studies.

Markers researchers commonly monitor

Study measures; no home-monitoring context exists.

Marker	Why it's watched
Blood pressure and heart rate	hypotension and flushing are the dose-limiting effects.
Cardiac output / cardiac index and systemic vascular resistance	the primary pharmacodynamic endpoints in the heart-failure studies.
ACTH and cortisol	the point of using a CRF-R2-selective peptide is that these should move little; measuring them tests that claim.
Plasma renin, aldosterone and NT-proBNP	all were suppressed by urocortin 2 in the human studies and serve as pathway readouts.
Creatinine, eGFR and urine sodium	the renal effects are a distinctive part of the profile.
Glucose	CRF-family signalling and urocortin 3's islet role make this worth tracking in any metabolic study.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Not applicable as a consumer practice. Urocortins are handled as research-grade peptides prepared for intravenous administration in instrumented clinical studies, with continuous blood-pressure monitoring because hypotension is the limiting effect. No established vial format, no community practice, no calculator preset.

6Commonly studied alongside

Serelaxin (#154) and adrenomedullin (#151) — the same acute-heart-failure vasodilator wave; apelin (#152) as another energy-efficient inotrope; natriuretic peptides. On the stress side, CRF itself and CRF-R1 antagonists.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Not FDA-approved; investigational
European Union	Not authorised
United Kingdom	Not licensed
Australia	Not approved
South Africa	Not registered
Sport	Not specifically listed by WADA by name; as non-approved peptide hormones the urocortins would fall under S0 if used. Check the current list

8Open questions

Does acute CRF-R2 agonism translate into any outcome benefit in heart failure, or does it join the long list of acute inotrope-vasodilators that improved numbers and not lives?
Can urocortin 2's renal and neurohormonal effects be sustained without tachyphylaxis?
What is urocortin 3's role in human islet function and in type 2 diabetes?
Why did pharmacological work on the CRF-R1 side of this family fail so comprehensively in mood disorders?

9References

1Vaughan J et al. (1995). Urocortin, a mammalian neuropeptide related to fish urotensin I and to corticotropin-releasing factor. Nature. PubMed · DOI
2Reyes TM et al. (2001). Urocortin II: a member of the corticotropin-releasing factor (CRF) neuropeptide family that is selectively bound by type 2 CRF receptors. Proc Natl Acad Sci USA. PubMed · DOI
3Lewis K et al. (2001). Identification of urocortin III, an additional member of the corticotropin-releasing factor family with high affinity for the CRF2 receptor. Proc Natl Acad Sci USA. PubMed · DOI
4Davis ME et al. (2007). Urocortin 2 infusion in human heart failure. Eur Heart J / J Am Coll Cardiol [verify journal]. PubMed · DOI
5Davis ME et al. (2005). Urocortin 1 infusion in normal humans. J Clin Endocrinol Metab. PubMed · DOI
6Rademaker MT, Richards AM (2017). Urocortins: actions in health and heart failure. Clin Chim Acta. PubMed · DOI
7van der Meulen T et al. (2015). Urocortin3 mediates somatostatin-dependent negative feedback control of insulin secretion. Nat Med. DOI

† Being confirmed by our reviewers against current sources.

10Community

forum threads →

community protocols include this →

Threads and protocols are visible to members. Joining is free.

Self-reported side effects Phase 2

Not enough data yet. 0 of the 50 members needed have logged this compound for 4+ weeks. We don't show anything below 50, so no one can be identified.

11Page history

30 Oct 2026Profile published — awaiting medical review

Licensed CC BY-NC-SA 4.0. Found an error? Report it · Editorial standards — corrections are logged here.