Expression of human placental D2-dopamine receptor during normal and abnormal pregnancies

Previous studies have demonstrated the presence of D2-dopamine binding sites in the human placenta, and that dopamine (DA), via these D2-like receptors, inhibits both basal- and hormone-stimulated secretion of human placental lactogen (hPL) from trophoblastic cells. However, nothing is known about the ontogenesis of this placental D2-dopamine receptor (D2R) during pregnancy. Therefore, the aim of this study was to analyse the expression of these receptors throughout gestation in placentae from normal as well as abnormal pregnancies. Western and Northern blot analysis were performed on membrane protein and messenger RNA (mRNA) preparations of human placentae from various weeks of gestation as well as from pregnancies complicated by pre-eclampsia of hydatidiform mole. The autoradiographs of both proteins and mRNA showed differential expression of placental D2R during normal pregnancy. When the relative levels of D2R proteins were analysed throughout pregnancy, there was a significant but transient decrease of approximately 23 per cent of D2R content at 9-16 weeks of gestation with a return to baseline levels at 17-18 weeks. An increase in mRNA levels began at week 19 of gestation and reached a maximum value at term. During the first half of gestation, the relative levels of D2R mRNA (2.5 kb) showed an inverse pattern of expression when compared to D2R protein content. Specifically, the levels of D2R mRNA increased by approximately 26 per cent between weeks 9 and 16 of pregnancy in comparison with the values observed at 7-8 weeks, and returned to baseline levels at 17-18 weeks of gestation. The D2R relative protein levels subsequently increased from 19 to 30 weeks of gestation, and then remained stable. The autoradiographs of both proteins and mRNA showed significantly decreased expressions in placentae from both pre-eclamptic (approximately 45 per cent inhibition) and molar (approximately 0-70 per cent inhibition) pregnancies. Moreover, there was important variability in the expression of placental D2R from hydatidiform moles. Using immunological and molecular biology techniques, the present study confirms the presence of D2R in human placenta. The variations of placental D2R expression during normal and abnormal pregnancies argue for an important role of DA in human placental function, although this remains to be investigated further.