Role of urocortin in pregnancy: An update and future perspectives

Table 1 Corticotropin-releasing factor, urocortin, corticotropin-releasing factor receptor 1 and 2 actions during pregnancy and labor

Peptide	Actions during pregnancy and labor
CRF	It is present in the syncytiotrophoblasts and intermediate trophoblasts during early implantation, and allows the necessary dilation of uterine and placental vessels The circulating concentration of CRF increases progressively during pregnancy At the end of pregnancy, the levels of CRF-binding protein fall dramatically, so the concentration of free CRF increases: this causes the stimulation of uterine smooth muscle contractions and the triggering of labor
UCN	UCN stimulates the secretion of ACTH and prostaglandin PGE2 by the trophoblast and has a vasodilatory effect on the placenta It induces uterine contractions by increasing myometrial contractile response to prostaglandins The levels of circulating UCN are higher during preterm labor, suggesting a key role of this peptide in triggering this condition
CRF-R1	During early implantation, the binding of CRF to CRF-R1 induces the expression of apoptotic FasL on invasive extravillous trophoblast and maternal decidual cells, allowing the physiological immune tolerance at the fetal-maternal interface It is strongly upregulated in the myometrium and fetal membranes during labor
CRF-R2	It is expressed in cultured extravillous trophoblasts at both mRNA and protein levels Its interaction with CRF and UCN may inhibit angiogenesis during early placentation

ACTH: Adrenocorticotropic hormone; CRF: Corticotropin-releasing factor; UCN: Urocortin; CRF-R1: Corticotropin-releasing factor receptor 1; CRF-R2: Corticotropin-releasing factor receptor 2.