ETHANOL HAS DIRECT EFFECTS ON HUMAN CHORIOCARCINOMA CELL STEROID-HORMONE SECRETION

Clinical observations indicate that ethanol (EtOH) consumption has sig nificant detrimental effects on pregnancy. However, there is a paucity of information on effects of EtOH on human placental function. We hav e used JEG choriocarcinoma cells that have many of the functional capa bilities of syncytiotrophoblasts, as a model to study direct effects o f EtOH on placental function. Between 20-100 mM EtOH decreased rate of cell growth by 25%, but no decrease in [S-35]methionine incorporation into protein was noted. EtOH decreased in a dose-dependent manner the secretion of progesterone (P-4) in response to cAMP when added with c AMP or when cells were pretreated with EtOH for 2 days. But after 4 or 6 days of pretreatment with EtOH, the P-4 response to cAMP was increa sed by EtOH. Furthermore, EtOH increased the stimulation of P-4 secret ion by Forskolin. The development of this response was dependent on th e period of exposure to EtOH. EtOH also increased estradiol (E(2)) sec retion by unstimulated JEG cells in a dose- and time-dependent manner and increased cAMP stimulated E(2) secretion > 2-fold following 4 days of pretreatment with EtOH. These results suggest that EtOH may direct ly alter hormone secretion by placental cells and such perturbations o f endocrine function of the placenta may be responsible for some of th e effects of EtOH on pregnancy.