Localization and characterization of urocortin during human pregnancy

Urocortin, a recently identified peptide of the corticotropin releasing hor mone (CRH) peptide family, has patent vasodilatory effects in the human fet al placental circulation in vitro, promoting us to hypothesize that urocort in is produced locally to regulate uteroplacental vascular tone during preg nancy. In the present study, we examined the distribution of urocortin in t he human placenta, fetal membranes and uterine tissue at term in the presen ce and absence of labour, using a urocortin antibody produced in our labora tory and the immunoperoxidase staining method. Immunoreactive (IR)-urocorti n was observed in the vascular smooth muscle of the myometrium (n=5), decid ual stromal cells, syncytiotrophoblast and amnion epithelium (n=10). No dif ferences in staining intensity for urocortin were detected between tissues obtained in the absence (n=5) or presence (n=5) of labour. Staining intensi ty for IR-urocortin was greatest in the decidua suggesting this may be a si te of urocortin production during pregnancy. Subsequently, we tested urocor tin secretion from chorio-decidual cells in vitro, using an immunoblot tech nique. Positive staining for urocortin was observed in 40 per cent of chori o-decidual cells with 34 per cent of these cells secreting urocortin under basal conditions. Since urocortin was secreted by decidual cells we questio ned whether urocortin was present in maternal plasma throughout gestation, using radioimmunoassay. Urocortin was detectable in maternal plasma from 7 weeks of gestation and concentrations did not change as gestation progresse d. IR-urocortin in the maternal plasma eluted from a Sephadex G-50 column a t the same site as synthetic urocortin and had a calculated retention coeff icient (Kd) of 0.44. In summary, this study indicates that urocortin is pro duced by the decidua during human pregnancy and is detectable in maternal p lasma. These data are consistent with the hypothesis that urocortin is prod uced locally by the decidua and may act to regulate uteroplacental blood fl ow. (C) 2000 Harcourt Publishers Ltd.