{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nUrocortin 3 (UCN3), a member of the corticotropin‐releasing factor (CRF) peptide family and a selective ligand for CRF receptor type 2, has been implicated in central neuromodulation. Genetic studies have linked UCN3 with major depressive disorder and shown that its expression or structural modifications can influence antidepressant response and ameliorate memory deficits, while electrophysiological studies indicate that UCN3 modulates neuronal excitability through CRF receptors and associated GIRK channel activation. These findings support a role for UCN3 in stress responsiveness, mood regulation, and cognitive processes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn peripheral tissues, UCN3 plays crucial roles in cardiovascular and metabolic regulation. In pancreatic islets UCN3 is stored in mature β‐cells and is co‐released with insulin where it potentiates glucose‐stimulated somatostatin secretion from δ‐cells, establishing a negative feedback loop essential for glycemic control and serving as a marker for β‐cell maturity. UCN3 is also expressed in the heart, kidney, adrenal glands, and placenta, where its paracrine actions evoke cardioprotective effects and participate in the response to hypoxic stress. Furthermore, altered UCN3 expression has been observed in heart failure and metabolic disorders, underscoring its role in maintaining organ homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nUCN3 also exerts important modulatory effects in reproductive and other peripheral systems. It is expressed in adipose tissue and the gastrointestinal tract – where it regulates angiogenic mediators such as VEGF‐A – as well as in the endometrium, placenta, and ovarian cells, modulating cytokine secretion and steroidogenesis. 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