Urocortin 2 (UCN2)

Urocortin 2 is an endogenous peptide encoded by the UCN2 gene in humans and other mammals, structurally related to corticotropin-releasing factor and primarily binding the CRH type 2 receptor (CRHR2) with high selectivity. In the periphery, it regulates cardiovascular function by enhancing cardiac contractility, reducing fatigue, and promoting anabolic and anti-catabolic responses in skeletal muscle through activation of cAMP, Akt, mTOR, and ERK1/2 pathways. Urocortin 2 also modulates insulin sensitivity and glucose metabolism, potentially influencing metabolic diseases, and exerts central nervous system actions involved in stress responses and appetite regulation. Its pleiotropic pathway effects suggest therapeutic potential in cardiac, muscle, and metabolic disorders, but safety concerns such as arrhythmogenic risks and receptor desensitization must be addressed in clinical development.

Other names

UCN2Urocortin IIStresscopin-related peptide

As an agonist of CRHR2, Urocortin 2 activates the Gs/cAMP/PKA pathway, stimulating downstream signaling including phosphorylation of Akt, mTOR, ERK1/2, and endothelial nitric oxide synthase (eNOS). Acute administration increases cAMP and can transiently induce insulin resistance, while chronic administration leads to CRHR2 desensitization and improved glucose tolerance.