Placental Urocortins and CRF in Late Gestation

Placental corticotropin-releasing factor (CRF) are thought to induce labor via activation of CRF receptor type 1 (CRF-R1) leading to several feed forward mechanisms in the placental, fetal and maternal compartments. Recently, receptor type 2 (CRF-R2) selective ligands called urocortin 2 and 3 (Ucn 2, Ucn 3) were characterized as neuropeptides in the brain. We studied the expression of Ucn 1, 2 and 3 in feto-placental tissues qualitatively (by immunohistochemistry) and quantitatively (by radioimmunoassay) and compared these with expression of placental CRF. The presented placental Ucn 2 and 3 peptide quantification, characterization and ex-vivo release results are novel. Reversed-phase HPLC fractionation of placental extracts revealed several peaks containing immune-reactive (ir)-like Ucn 2 or 3, of which the main peaks had the same retention time as the synthetic Ucn 2 and 3 peptides. Placental tissues contained between 6 and 10 times more ir-CRF than ir-Ucn 1, 2 or 3. The placental Ucn 1, 2 and 3 peptide contents correlated with each other. Our immunohistochemical results showed that all urocortins were mainly localized in the syncytiotrophoblasts of the placental villi. Placental urocortins were actively released during ex-vivo perfusion of cotyledons. From these results it can be concluded that Ucn 2 and 3 peptides are present in placental and fetal membrane tissues, and released by ex-vivo perfused cotyledons. Therefore, placental urocortins may function as paracrine or endocrine messengers during pregnancy and parturition.