Chronic ethanol exposure inhibits insulin and IGF-1 stimulated amino acid uptake in cultured human placental trophoblasts.
Maternal alcohol abuse during pregnancy can lead to abnormalities in fetal development, sometimes manifested as the fetal alcohol syndrome (FAS). Although intrauterine growth retardation is a hallmark of FAS, the pathophysiology is not fully understood. A contributing factor may be altered placental function. In this study, the effect of long-term exposure to ethanol on subsequent amino acid uptake by the cultured human placental trophoblasts was examined. Both Na(+)-dependent and Na(+)-independent pathways for AIB uptake were measured. As reported previously, insulin and IGF-1 enhanced Na(+)-dependent AIB uptake. Exposure to ethanol had no effect on basal (nonhormone treated) AIB uptake. However, 72-hr ethanol pretreatment of trophoblasts inhibited Na(+)-dependent AIB uptake under stimulation by insulin or IGF-1 in the absence of ethanol. Na(+)-independent uptake was not affected. Ethanol treatment had no effect on insulin or IGF-1 binding to cultured trophoblasts. These findings suggest that 72-hr ethanol treatment in cultured trophoblasts may affect postreceptor signal transduction in the insulin or IGF-1 pathways. Such changes have implications for the effect of ethanol on normal function of the human placenta, the major interface for maternal/fetal transfer of nutrients.
Karl
P I
PI
Department of Pediatrics, North Shore University Hospital, Cornell University Medical College, Manhasset, New York 11030.
Fisher
S E
SE
D000596:Amino Acids / Q000378:metabolism*; D000621:Aminoisobutyric Acids / Q000378:metabolism; D046508:Culture Techniques; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000503:physiopathology; D006801:Humans; D007231:Infant, Newborn; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008431:Maternal-Fetal Exchange / Q000187:drug effects / Q000502:physiology; D010920:Placenta / Q000187:drug effects* / Q000503:physiopathology; D011247:Pregnancy; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D012964:Sodium / Q000502:physiology; D014327:Trophoblasts / Q000187:drug effects*
D000596:Amino Acids; D000621:Aminoisobutyric Acids; D007328:Insulin; C100049:2-aminoisobutyric acid; D000431:Ethanol; D007334:Insulin-Like Growth Factor I; D012964:Sodium