Urocortin 3
An endogenous 38-amino-acid neuropeptide that selectively switches on the CRF type 2 receptor; a local islet brake on insulin and glucagon and a stress-axis signal — studied in the lab, not a drug
Urocortin 3 (UCN3), also called stresscopin, is a small human neuropeptide identified in 2001 as the newest member of the corticotropin-releasing factor (CRF) family. Unlike CRF itself, UCN3 acts almost exclusively through one receptor — the CRF type 2 receptor (CRHR2) — which gives it a distinct, targeted set of jobs. In the pancreatic islet it is made by insulin and glucagon cells and signals to the neighbouring somatostatin-producing delta cells, turning up the somatostatin 'brake' that fine-tunes how much insulin and glucagon are released; it is also a hallmark that a beta cell has matured. In the brain and body it is part of the stress response, expressed in the hypothalamus, adrenal gland, gut and placenta. UCN3 is an endogenous peptide studied as a research tool and biomarker; it is not an approved medicine and has not been given to people as a treatment.
No established human dose Details ↓
Recommended Dosing
No established human dose
Urocortin 3 is an endogenous human neuropeptide that has never been given to people as a treatment. It is studied as a local islet signal, a stress-axis peptide and a candidate biomarker measured in blood and urine, not as an administered drug.
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What is it?
Urocortin 3 belongs to the corticotropin-releasing factor (CRF) family — the same family as CRF itself, the master hormone that starts the body's stress response, and the other urocortins (urocortin 1 and urocortin 2). It was the last of the three urocortins to be found, identified in human tissue in 2001 and also named 'stresscopin'. What sets it apart is receptor selectivity: where CRF and urocortin 1 hit both CRF receptor types, urocortin 3 acts almost only through the CRF type 2 receptor (CRHR2), so it reports specifically on CRHR2 biology.
Its best-characterised modern role is inside the pancreatic islet. Urocortin 3 is stored in human insulin (beta) and glucagon (alpha) cells and is released alongside those hormones. It then acts locally on the islet's somatostatin-producing delta cells, which carry CRHR2, prompting them to release somatostatin. Somatostatin is the islet's own negative-feedback signal, so urocortin 3 effectively tunes the brake that stops insulin and glucagon output from running too high — a fine local control loop rather than a long-range hormone.
Urocortin 3 is also a sign of a healthy, grown-up beta cell. It appears only once a beta cell has matured and can secrete insulin properly, and it falls away when beta cells de-differentiate or fail. For that reason researchers use urocortin 3 as a readout of beta-cell maturity and function in diabetes research, not as something to give.
Beyond the islet, urocortin 3 is part of the wider stress and neuroendocrine system. It is expressed in discrete brain regions — including hypothalamic areas that govern stress, feeding and social behaviour — and in peripheral tissues such as the adrenal gland, the large intestine and the placenta, where it is thought to act as a local (autocrine or paracrine) modulator during stress. In mice, a specific group of urocortin-3 neurons in the hypothalamus was shown to carry the effect of chronic stress on how females behave toward infants.
Because the CRF type 2 receptor is protective in the heart and brain, the urocortin family has drawn interest as experimental protectants, and urocortin 3 has been studied in local systems such as the human ovary, where a stresscopin/CRHR2 loop lowers progesterone output. These are mechanistic laboratory findings that map out what the peptide does, not human therapies.
Urocortin 3 is an endogenous human neuropeptide and a research and biomarker tool, not a medicine. No published study has given urocortin 3 to people as a treatment, it is approved nowhere, and material sold online as 'stresscopin' or 'UCN3' is an unregulated research chemical. Nothing here is a dose or a therapy; this page records what the published science says about the peptide.
Mechanism of Action
Urocortin 3 is a CRF-family peptide that works through one receptor, CRHR2. In the islet it drives a local somatostatin brake on insulin and glucagon and marks mature beta cells; in the brain, adrenal and gut it is a local stress-response signal.
Islet somatostatin feedback
Released from pancreatic beta and alpha cells, urocortin 3 acts on CRHR2 on neighbouring delta cells to potentiate somatostatin release, the islet's own negative-feedback brake that restrains insulin and glucagon output; its presence also marks a matured beta cell (PMID 35065098).
Stress-axis and tissue signalling
Urocortin 3 is expressed in stress-related hypothalamic neurons and in the adrenal gland, colon and placenta, acting as a local autocrine/paracrine modulator; in mice, hypothalamic urocortin-3 neurons carry chronic-stress effects on behaviour (PMIDs 16095756, 15949638, 36476733).
Published Research
These are studies of urocortin 3 read from their PubMed abstracts on November 6, 2026. They cover its role as a local inducer of islet somatostatin and a marker of beta-cell maturity, its biology and CRHR2 receptor axis as a stress biomarker, its expression in human adrenal gland and colon, a mouse study placing urocortin-3 neurons at the centre of chronic-stress effects on behaviour, and a rat study of the urocortins as neuroprotectants. Urocortin 3 has not been given to people as a treatment in any published study.
Local inducer of somatostatin and bellwether of beta-cell maturity
A mechanistic review of urocortin 3 in the pancreatic islet. UCN3 is expressed in human alpha and beta cells (and in mouse beta cells), and signals locally through CRHR2 on delta cells to potentiate somatostatin negative feedback, which restrains insulin and glucagon output. UCN3 appears as beta cells mature (raising their glucose threshold for insulin release) and is downregulated in de-differentiated, dysfunctional beta cells — making it both a tuner of islet hormone output and a marker of beta-cell maturity and health.
The urocortin peptides: UCN3, its receptor, and biomarker aspects
A review of the urocortin family focused on urocortin 3 and the CRF type 2 receptor (CRHR2) as a regulatory axis for the stress response. It links dysregulation of the UCN3/CRHR2 axis to stress-related conditions — post-traumatic stress, sleep apnea and cardiovascular disease — and discusses measuring UCN3 in blood and urine as a potential laboratory biomarker of stress homeostasis.
Expression in human adrenal glands and tumors
Immunoreactive urocortin 3 / stresscopin was found at high concentration in normal human adrenal glands — higher than in brain — and in aldosterone- and cortisol-secreting adenomas and pheochromocytomas, with UCN3 mRNA confirmed by RT-PCR. The authors concluded UCN3 is produced in the adrenal and acts as a local autocrine or paracrine regulator, part of the adrenal stress system.
Urocortin 3 / stresscopin in the human colon
Urocortin 3 was localised in the myenteric and submucosal nerve plexuses, vascular cells, smooth muscle and enterochromaffin cells of the normal human large intestine, with its CRHR2 receptor co-expressed, and immunoreactive UCN3 measured at highest levels in the rectum and sigmoid colon. The pattern — distinct from urocortin 1 — suggests UCN3 modulates gut function under stressful conditions.
Urocortin-3 neurons and chronic stress on infant-directed behavior (mice)
In mice, urocortin-3-expressing neurons of the perifornical hypothalamus became more active with infant-directed behaviour and with chronic restraint stress. Chemogenetically silencing these neurons improved pup retrieval in virgin females and blocked the stress-induced deficit in pup-directed behaviour, identifying urocortin-3 neurons as critical mediators of how chronic stress shapes female infant-directed behaviour — a mechanistic animal result.
Stresscopin / urocortin 3 suppresses progesterone in human ovarian cells
In cultured human granulosa-lutein cells from infertile women, both urocortin 3 / stresscopin and its CRHR2 receptor were present, and UCN3 was detectable in follicular fluid. Treating the cells with urocortin 3 lowered progesterone secretion, and a CRHR2 antagonist reversed the effect — evidence that a local stresscopin/CRHR2 system acts in the human ovary, a mechanistic human-cell study rather than a therapy.
No Established Human Dose
Urocortin 3 is an endogenous human neuropeptide that has never been given to people as a treatment. It is studied as a local islet signal, a stress-axis peptide and a candidate biomarker measured in blood and urine, not as an administered drug. No regulator has approved any dose, and animal and cell studies used recombinant urocortin 3 at experimental amounts that do not carry over to people, so no amount is printed here.
What this rests on: PMID 35738909, PMID 35065098, PMID 19351656.
Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes Urocortin 3 is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
Unknown: no human dose of Urocortin 3 has been established (see No Established Human Dose below), so there is no amount to work out. The reconstitution calculator does the arithmetic for any vial, water and dose.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Urocortin 3, before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long Urocortin 3 stays intact once mixed.
How it is taken
Unknown: with no established human dose, there is no established way of taking Urocortin 3. What the human studies gave and how is set out under No Established Human Dose.
What to expect, and when
How long it stays in the body: a half-life of not established for humans; an endogenous locally acting neuropeptide. After about five half-lives almost none is left.
When effects appear: unknown; no source on this page gives a time to effect for Urocortin 3. Results reported in the studies are under Published Research.
Source: half-life: PMID 35738909.
Side effects, and when to stop or get help
From the Side Effects section: No human adverse-event data exist: no published study has administered urocortin 3 to people; It is a local islet and stress-axis signal measured in tissue and body fluids, not a therapy (PMIDs 35065098, 35738909); Animal and human-cell work used recombinant urocortin at experimental concentrations that do not translate to human dosing (PMIDs 36476733, 19351656); Material sold online as 'stresscopin' or 'UCN3' is an unregulated research chemical of unverified content. Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Urocortin 3. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“Urocortin 3 is an endogenous peptide that has not been given to people as a drug, so there is no human safety profile; the points below reflect that research status”).
Interactions
Unknown: a PubMed search for human interaction studies of Urocortin 3 (reviewed 2026-11-06) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Urocortin 3 products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Research Chemical (Not a drug: Drugs@FDA and the openFDA label endpoint hold no record, and FDA GSRS and ChEMBL hold no substance record for urocortin 3 / stresscopin (searched November 6, 2026)). Sport: Not on the 2026 List.
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
Urocortin 3 is an endogenous peptide that has not been given to people as a drug, so there is no human safety profile; the points below reflect that research status.
Contraindications & Cautions
Urocortin 3 has no approved use and no label. These points reflect its endogenous, research status.
Legal Status
Urocortin 3 (stresscopin) is an endogenous human neuropeptide studied as a research compound and biomarker; it is not a drug and is not approved in any country.
Frequently Asked Questions
?What is urocortin 3?
An endogenous human neuropeptide, also called stresscopin, identified in 2001 as the newest member of the corticotropin-releasing factor (CRF) family. It is a 38-amino-acid peptide that acts selectively through the CRF type 2 receptor (CRHR2).
?What does it do?
In the pancreatic islet it triggers delta cells to release somatostatin, the brake that restrains insulin and glucagon, and it marks a mature beta cell (PMID 35065098). It is also a stress-axis signal expressed in the brain, adrenal gland, gut and placenta (PMIDs 16095756, 15949638, 35738909).
?Is it a diabetes drug?
No. Urocortin 3 is used in diabetes research as a readout of beta-cell maturity and islet feedback, not as a treatment. No human trial has given urocortin 3 to people, and it is approved nowhere.
?Is it approved or available to buy?
No. Urocortin 3 is not a medicine, has no FDA application or label, and is approved nowhere. Material sold online as 'stresscopin' or 'UCN3' is an unregulated research chemical. Grey Peptides lists no sellers and recommends no source; this page records the published science.
References
- [review] Flisher MF, et al. "Urocortin3: Local inducer of somatostatin release and bellwether of beta cell maturity." Peptides, 2022;151:170748. PMID: 35065098.
- [review] Alghamdi NJ, et al. "The urocortin peptides: biological relevance and laboratory aspects of UCN3 and its receptor." Crit Rev Clin Lab Sci, 2022;59(8):573-585. PMID: 35738909.
- [mechanism] Takahashi K, et al. "Expression of urocortin 3/stresscopin in human adrenal glands and adrenal tumors." Peptides, 2006;27(1):178-82. PMID: 16095756.
- [mechanism] Saruta M, et al. "Urocortin 3/stresscopin in human colon: possible modulators of gastrointestinal function during stressful conditions." Peptides, 2005;26(7):1196-206. PMID: 15949638.
- [animal] Abdelmesih B, et al. "Urocortin-3 neurons in the perifornical area are critical mediators of chronic stress on female infant-directed behavior." Mol Psychiatry, 2023;28(1):483-496. PMID: 36476733.
- [mechanism] Yata A, et al. "Suppression of progesterone production by stresscopin/urocortin 3 in cultured human granulosa-lutein cells." Hum Reprod, 2009;24(7):1748-53. PMID: 19351656.
- [other] UniProt Q969E3 (UCN3_HUMAN), read November 6, 2026: urocortin 3 is the product of the UCN3 gene (aliases stresscopin / SCP / UCNIII), a secreted 38-amino-acid neuropeptide of the corticotropin-releasing factor family and a selective endogenous agonist of the CRF type 2 receptor (CRHR2). https://www.uniprot.org/uniprotkb/Q969E3/entry
- [other] Human urocortin 3 / stresscopin was identified in 2001 as a selective ligand for the type 2 corticotropin-releasing hormone receptor, the newest member of the urocortin family; its biology and CRHR2 axis are summarized in the reviews carded on this page (read November 6, 2026).
- [other] US FDA, Drugs@FDA and the drug label endpoint (openFDA), searched November 6, 2026: no application and no label record for urocortin 3 / stresscopin. It is an endogenous human neuropeptide, not a registered drug; FDA GSRS and ChEMBL hold no substance record for it.
Sources & Citations
The six studies carded above were read from their PubMed records on November 6, 2026. Identity comes from UniProt (Q969E3, gene UCN3); urocortin 3's 2001 identification and its CRHR2 axis are summarized in the reviews carded here; the absence of US approval and of a drug substance record from Drugs@FDA, openFDA, FDA GSRS and ChEMBL was checked the same day. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.