What Is Urocortin II? Definition and What Research Reports

Definition

Urocortin II is a naturally occurring mammalian peptide belonging to the corticotropin-releasing factor (CRF) family, a group that also includes CRF itself, urocortin (urocortin I) and urocortin III. It is sometimes referred to in the literature by the alternate name stresscopin-related peptide. Its defining pharmacological feature is receptor selectivity: researchers reported that short three-amino-acid motifs within the sequences of urocortin II and urocortin III determine their preference for the CRF receptor type 2 (CRF2) subtype rather than CRF receptor type 1 (PMID 15223302). Because of that selectivity, the term "urocortin II" appears in the literature both as the name of an endogenous signalling peptide and as the name of a laboratory tool used to probe what CRF2 receptors do in a given tissue.

What Class of Molecule Is It?

Urocortin II is a peptide hormone / neuropeptide — a short chain of amino acids rather than a steroid, small molecule or antibody. It is a paralogue of CRF, meaning it arose from the same ancestral gene family and shares enough structural similarity to bind CRF-family receptors, while differing enough to discriminate between receptor subtypes (PMID 15223302). Like other peptides in this family, it is generated in tissue as a precursor that is processed to the mature peptide.

Where It Comes From in the Body

• Central nervous system. The study of stress and adrenalectomy in rats examined urocortin II mRNA expression in the hypothalamic paraventricular nucleus, a core stress-response region (PMID 12869794).
• Reproductive tissue. Researchers reported that human endometrium expresses urocortin II and urocortin III messenger RNA and the corresponding peptides (PMID 17074339), and a separate report described urocortin II expression in human pregnant myometrial cells (PMID 14592950).
• Cardiovascular tissue. Work in cardiac myocytes examined urocortin II signalling in the heart and in heart failure models (PMID 24441548), and endothelial cell experiments reported urocortin II–driven nitric oxide production (PMID 19255503).

How the Term Is Used in Peptide Research

In published research, "urocortin II" is used in three distinguishable ways. First, as an endogenous ligand whose tissue expression is mapped and whose regulation is measured — for example, the study that tracked urocortin II mRNA in the rat paraventricular nucleus following stress and adrenalectomy treated it as a stress-regulated transcript (PMID 12869794). Second, as a selective CRF2 agonist tool: because urocortin II discriminates between CRF receptor subtypes (PMID 15223302), applying it to a preparation is a way of asking what CRF2 activation alone does, which is how researchers established an endogenous cardioprotective role for CRF receptor type 2 in the murine heart (PMID 12970163). Third, as a comparator against urocortin I or CRF, used to attribute an effect to one receptor subtype rather than another.

Urocortin II is not an approved medicine in the United States; peptides of this kind are handled in published work as research materials in animal, tissue and cell-culture experiments. This page is for educational purposes only and is not medical advice; consult a licensed physician about any health decision. Nothing here describes a protocol, and the studies summarised below were conducted in laboratory models, not as consumer use.

What the Published Literature Reports

Heart and Coronary Circulation

Cardiac work forms the largest single cluster. Researchers reported that urocortin II and urocortin III were cardioprotective against ischaemia–reperfusion injury and described an essential endogenous cardioprotective role for CRF receptor type 2 in the murine heart (PMID 12970163). At the transcriptional level, a later report examined NFAT transcription factor regulation by urocortin II in cardiac myocytes and in heart failure (PMID 24441548). In a whole-animal preparation, the study of urocortin II administration in the anaesthetised pig reported effects on the coronary circulation and cardiac function that were nitric-oxide-dependent (PMID 17936748).

Endothelium and Vascular Wall

In cultured endothelial cells, researchers reported that urocortin II induced nitric oxide production through cAMP- and Ca²⁺-related pathways (PMID 19255503), which is mechanistically consistent with the nitric-oxide dependence observed in the porcine coronary work (PMID 17936748). A more recent paper examined molecular mechanisms and effects of urocortin II on rat adventitial fibroblast calcification induced by calcified medium (PMID 36083783).

Skeletal Muscle

One endocrinology report examined urocortin II treatment in skeletal muscle and described reduced loss of muscle mass and function during atrophy, together with increased mass and function in non-atrophying skeletal muscle (PMID 12960070).

Gastrointestinal Tract

Researchers investigated the role of peripheral corticotropin-releasing factor and urocortin II in intestinal inflammation and motility in the terminal ileum (PMID 15883387), placing the peptide within the broader literature on CRF-family signalling in gut function.

Uterus and Endometrium

Beyond simple expression mapping, the study of human pregnant myometrial cells reported that urocortin II regulated myosin light chain phosphorylation and discussed a potential role for the type-2 corticotropin-releasing hormone receptor in the control of myometrial contractility (PMID 14592950). Endometrial expression of both urocortin II and urocortin III was documented at the mRNA and peptide level (PMID 17074339).

Neurons

Not every CRF-family peptide behaved alike in neural preparations. Researchers reported that urocortin, but not urocortin II, protected cultured hippocampal neurons from oxidative and excitotoxic cell death, and attributed that protection to corticotropin-releasing hormone receptor type 1 (PMID 11784785). That negative result is often cited as a practical illustration of receptor-subtype selectivity in action.

Research Contexts at a Glance

Safety and Adverse Events: What Studies Report

The verified literature summarised on this page is preclinical and mechanistic. These reports were designed around expression, receptor selectivity and physiological endpoints in animals and cultured cells — for example ischaemia–reperfusion injury in the murine heart (PMID 12970163) or coronary responses in the anaesthetised pig (PMID 17936748) — rather than as human safety or tolerability trials, and they do not establish a safety profile in people. Findings in rodent, porcine and cell-culture systems do not automatically transfer to humans, and a peptide that acts on vascular tone and nitric oxide production in one preparation (PMID 19255503) may behave differently in another. Anyone with questions about CRF-family signalling and their own health should raise them with a licensed clinician.

Related Terms

• CRF / CRH — the parent peptide of the family, studied alongside urocortin II in intestinal work (PMID 15883387).
• Urocortin (urocortin I) — a related peptide that, unlike urocortin II, protected hippocampal neurons in one report (PMID 11784785).
• Urocortin III — co-expressed with urocortin II in human endometrium (PMID 17074339) and similarly CRF2-selective (PMID 15223302).
• CRF receptor type 2 (CRF2 / CRHR2) — the receptor subtype through which urocortin II effects are generally attributed (PMID 12970163).

References

• Three-amino-acid motifs of urocortin II and III determine their CRF receptor subtype selectivity (Neuropharmacology, 2004)
• Effect of stress and adrenalectomy on urocortin II mRNA expression in the hypothalamic paraventricular nucleus of the rat (Neuroendocrinology, 2003)
• Human endometrium expresses urocortin II and III messenger RNA and peptides (Fertility and Sterility, 2006)
• Urocortin II is expressed in human pregnant myometrial cells and regulates myosin light chain phosphorylation (Endocrinology, 2004)
• Urocortin-II and urocortin-III are cardioprotective against ischemia reperfusion injury (Endocrinology, 2004)
• NFAT transcription factor regulation by urocortin II in cardiac myocytes and heart failure (American Journal of Physiology. Heart and Circulatory Physiology, 2014)
• The effect of urocortin II administration on the coronary circulation and cardiac function in the anaesthetized pig is nitric-oxide-dependent (European Journal of Pharmacology, 2008)
• Urocortin II induces nitric oxide production through cAMP and Ca2+ related pathways in endothelial cells (Cellular Physiology and Biochemistry, 2009)
• Urocortin II treatment reduces skeletal muscle mass and function loss during atrophy and increases nonatrophying skeletal muscle mass and function (Endocrinology, 2003)
• Role of peripheral corticotropin-releasing factor and urocortin II in intestinal inflammation and motility in terminal ileum (PNAS, 2005)
• Urocortin, but not urocortin II, protects cultured hippocampal neurons from oxidative and excitotoxic cell death via corticotropin-releasing hormone receptor type I (Journal of Neuroscience, 2002)
• Molecular mechanisms and effects of urocortin II on rat adventitial fibroblast calcification induced by calcified medium (Vascular Biology, 2022)