EFFECT OF ETHANOL ON INSULIN-LIKE GROWTH FACTOR-II RELEASE FROM FETAL ORGANS

This study examines the effect of ethanol (ETOH) exposure and nutrient restriction on the release of insulin-like growth factor (IGF)-II from 18- and 20-day explanted fetal organs. Fetuses were exposed to ETOH (E) in utero by feeding dams a 36% (calories derived from ETOH: 6.6% v/v) ETOH liquid diet. Control fetuses were offsprings of dams either pair-fed (P) a control liquid diet or ad libitum (A) fed a standard pelleted lab chow. Blain, heart, kidney, liver, lung, muscle, and placenta of fetuses from the same litter were pooled and explanted, and IGF-II concentration in explanted media was analyzed by radioimmunoassay. Maternal and fetal weights were determined during pregnancy and at sacrifice, respectively, to evaluate the influence of ETOH on growth. Both maternal and fetal weights were substantially reduced by ETOH on 18 and 20 days of gestation compared with both A and P controls. At 18 days of gestation, E fetuses (1.33 +/- 0.03 g) weighed less than either A (1.47 +/- 0.03 g) or P (1.54 +/- 0.04 g) fetuses. By 20 days, A mean fetal weight (4.19 +/- 0.23 g) was significantly greater than both P (3.74 +/- 0.06 g) and E (3.28 +/- 0.06 g) fetuses. IGF-II concentration in media from 18-day fetal explants was highest from E (brain, heart, liver, and placenta) and P tissues (kidney, lung, and muscle). IGF-II in media from A tissues (except placenta) was lower than both E and P levels. A significant difference between treatments occurred in heart. By 20 days, IGF-II levels were highest in media from all A tissues (except placenta). IGF II in media from E tissues (except lung) was lower than those from P tissues. A significant difference between treatments occurred in the brain. With regard to the developmental pattern, IGF-II release generally increased between 18 and 20 days of gestation, with the greatest increases occurring in A tissues. Increased secretion by P tissues was greater than that by corresponding E tissues, and tended to follow the A trend. On the other hand, E brain, kidney, and placenta released only slightly more IGF-II at 20 days compared to 18 days, whereas E heart, liver, lung, and muscle released slightly less hormone. This study suggests that even moderate nutrient deprivation influences the pattern of IGF-II release from fetal organs, even though there is only a small decrease in overall body size. At the same level of nutrient deprivation, ETOH more dramatically alters both fetal weight and the pattern of IGF-II release. Because IGFs are autocrine/ paracrine factors that influence growth, differentiation, and function, the reduced availability of IGF-II may be one of the factors contributing to ETOH induced growth retardation and impaired functional capacity of some organ systems.