Placental urocortin-2 and -3: endocrine or paracrine functioning during healthy pregnancy?

OBJECTIVES

Placental urocortins may affect uterine quiescence by modulating in an endocrine or paracrine way the estradiol secretion by the adjacent placenta. The aim of this study was to investigate the role of placental urocortin-2 and -3 as endocrine or as auto/paracrine messengers in concert with placental estradiol generation.

STUDY DESIGN

In a cross-sectional study, plasma was obtained from healthy pregnant women, between 10 and 42 gestational weeks, and from nonpregnant women. Third trimester plasma pools were used for urocortin-2 and -3 peptide characterization by HPLC and RIA. Plasma samples (gestational age 10 and 42 wk) were analyzed using validated radioimmunoassays specific for urocortins and corticotropin-releasing factor (CRF). To reveal possible local actions of urocortins the influence of urcortin-2 on the estradiol secretion from placental tissue cultures was investigated.

RESULTS

Reversed-phase HPLC fractionation of plasma extracts revealed several peaks containing immunoreactive-like urocortin-2 or -3, of which the main peaks had the same retention time as the synthetic urocortin-2 or -3 peptides. In contrast to plasma CRF, no gestational age dependent changes in plasma urocortin-1, -2 and -3 levels occurred. The mean plasma urocortin levels during gestation did not differ from postpartum levels. In vitro, urocortin-2 stimulated dose-dependently the placental estradiol secretion, a stimulation inhibited by antisauvagine-30, a CRF-receptor 2 antagonist.

CONCLUSION

Placentas of healthy pregnant women do not, or not to any great extent, secrete urocortin-2 and -3 in the plasma. We show that urocortins can regulate the estradiol secretion from placental tissue cultures via the CRF-R2 mediated pathway. Therefore, placental urocortin-2 and -3 peptides are more likely to function as auto/paracrine messengers during healthy pregnancy, than as endocrine messengers.