Wimalasena J, Beams F, Caudle M R
Department of Obstetrics and Gynecology, University of Tennessee Medical Center-Knoxville 37920.
Alcohol Clin Exp Res. 1994 Dec;18(6):1448-55. doi: 10.1111/j.1530-0277.1994.tb01449.x.
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.
临床数据分析表明，乙醇（EtOH）是一种胚胎毒性剂，也是一种会破坏正常胎盘结构和功能的物质。由于表皮生长因子（EGF）是胎盘功能的重要调节因子，我们利用JEG-3绒毛膜癌细胞作为滋养层细胞模型，研究了EtOH对EGF诱导的激素分泌的影响。生理浓度（5-100 mM）的EtOH以时间和剂量依赖性方式调节EGF的作用。在用EtOH对细胞进行2天预处理后，20-100 mM的EtOH可增加EGF诱导的P4分泌，但6天预处理后则不会。用50 mM EtOH预孵育可使对50和100 ng/ml EGF的P4反应加倍。尽管用10-50 mM EtOH对细胞进行2天或4天预孵育可增加对20 ng/ml EGF的E2分泌，但6天预孵育会抑制对EGF的分泌反应。用10-50 mM（而非100 mM）EtOH对细胞进行2至6天预处理可增强人绒毛膜促性腺激素（hCG）对EGF的分泌反应。在50 mM EtOH时，对EGF的hCG分泌增加了2倍。EtOH还以剂量依赖性方式增加10-50 mM EtOH之间的基础hCG分泌。这些结果表明，EtOH可能调节源自胎盘的细胞中EGF刺激的激素分泌。如果这些改变发生在体内，可能会影响胎盘功能，并可能解释孕期酒精毒性的病理生理学。
