Alcohol-induced modulation of the insulin-like growth factor system in early chick embryo cranial tissue.

Abstract

Fetal alcohol exposure has been shown to reduce fetal/embryonic growth. The insulin-like growth factor (IGF) system plays a major role in normal growth and development of the embryo. The purpose of this study was to gain a better understanding of the effects of alcohol (ethanol, EtOH) exposure on the insulin-like growth factors, their binding proteins, and receptors during embryonic development. After the administration of either alcohol or chick Ringer's solution to individual eggs at the start of incubation, type-1 IGF receptors, IGF-binding proteins (IGFBPs) as well as IGF-1 and IGF-2 levels were measured in chick embryo craniums on days 5, 6, 7, and 8 of incubation. Levels of the IGF-1 receptor protein were not significantly different between treatment groups on any day studied. In EtOH-treated embryos, the 30 kDa IGFBP levels were significantly higher than vehicle levels on days 5 and 6. On day 6, IGF-1 levels were significantly lower in the alcohol-treated embryos compared with levels in vehicle-treated embryos of the same age. By day 8 of incubation, IGF-1 levels were significantly higher and the 30 kDa IGFBP levels were significantly lower in the alcohol-treated group compared with vehicles. These results indicate an initial EtOH-associated reduction in the amount of IGF-1 available to bind to its receptor (bioavailability), followed by increased IGF-1 bioavailability by day 8. The elevated IGFBP levels and reduced IGF-1 levels on days 5 and 6 of incubation are congruent with an overall reduction in the bioavailability of IGF-1 during this period and correlate with the decreased embryo weight observed in the alcohol-treated embryos. An increased bioavailability of IGF-1 observed by day 8 may represent a rebound effect and is associated with increases in ornithine decarboxylase activity, a marker of increased growth.