ETHANOL MODULATES THE HORMONE SECRETORY RESPONSES INDUCED BY EPIDERMAL GROWTH-FACTOR IN CHORIOCARCINOMA CELLS

Analysis of clinical data has implicated ethanol (EtOH) as an embryoto xic agent and as an agent that disrupts normal placental structure and function. Because epidermal growth factor (EGF) is an important regul ator of placental function, we have studied the effects of EtOH on EGF -induced hormone secretion using JEG-3 choriocarcinoma cells that serv e as a model for trophoblast cells. EtOH at physiological (5-100 mM) c oncentrations modulated effects of EGF in a time and dose-dependent ma nner. EGF-induced P-4 secretion was increased by 20-100 mM EtOH after a 2-day pretreatment of cells with EtOH, but not after a 6-day pretrea tment. Preincubation with 50 mM EtOH doubled the P-4 responses to 50 a nd 100 ng/ml EGF. Although a 2- or 4-day preincubation of cells with 1 0-50 mM EtOH increased the secretion of E(2) in response to 20 ng/ml E GF, a 6-day preincubation inhibited the secretory response to EGF. Pre treatment of cells with 10-50 mM, but not 100 mM EtOH for 2 to 6 days enhanced the human chorionic gonadotropin (hCG) secretory response to EGF. At 50 mm EtOH, the secretion of hCG in response to EGF was increa sed 2-fold. EtOH also increased basal hCG secretion in a dose dependen t manner between 10-50 mM EtOH. These results suggest that EtOH may mo dulate EGF-stimulated hormone secretion from cells of placental origin . Such alterations, if they occur in vivo, may impact on the function of the placenta and could potentially explain the pathophysiology of a lcohol toxicity during pregnancy.