Ethanol Modulates the Hormone Secretory Responses Induced by Epidermal Growth Factor in Choriocarcinoma Cells

Abstract

Analysis of clinical data has implicated ethanol (EtOH) as an embryotoxic agent and as an agent that disrupts normal placental structure and function. Because epidermal growth factor (EGF) is an important regulator of placental function, we have studied the effects of EtOH on EGF-induced hormone secretion using JEG-3 choriocarcinoma cells that serve as a model for trophoblast cells. EtOH at physiological (5-100 mM) concentrations modulated effects of EGF in a time and dose-dependent manner. EGF-induced P4 secretion was increased by 20-100 mM EtOH after a 2-day pretreatment of cells with EtOH, but not after a 6-day pretreatment. Preincubation with 50 mM EtOH doubled the P4 responses to 50 and 100 ng/ml EGF. Although a 2- or 4-day preincubation of cells with 10-50 mM EtOH increased the secretion of E2 in response to 20 ng/ml EGF, a 6-day preincubation inhibited the secretory response to EGF. Pretreatment 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 increased 2-fold. EtOH also increased basal hCG secretion in a dose-dependent manner between 10-50 mM EtOH. These results suggest that EtOH may modulate 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 alcohol toxicity during pregnancy.

Genomic Alterations in Ethanol-Exposed Trophoblast Cell Lines Induced by Chronic Ethanol Treatment

“…Cell cultures were maintained at 37°C in humidified 5% CO 2 atmosphere. These lines are the best characterized [9,19,20] and also allow chronic ethanol exposure during several hours as previously described [19,20].…”

The Placenta in Toxicology. Part IV

“…Thirty pesticides have been investigated for their ability to modulate aromatase activity in JEG-3 cells, 4 of which inhibit and 9 induce aromatase activity; another 4 induce CYP19 gene expression (Laville et al 2006). Jeg-3 cells have been used to demonstrate increased human choriogonadotropin (HCG) production when epidermal growth factor (EGF)–stimulated cells are additionally exposed to ethanol (Wimalasena, Beams, and Caudle 1994). …”