EFFECT OF IN-UTERO ETHANOL EXPOSURE ON THE POSTNATAL ONTOGENY OF INSULIN-LIKE GROWTH-FACTOR-I, AND TYPE-1 AND TYPE-2 INSULIN-LIKE GROWTH-FACTOR RECEPTORS IN THE RAT-BRAIN

There is convincing evidence that alcohol consumption during pregnancy causes major CNS abnormalities; however, the molecular and cellular b asis of these dysfunctions is currently not understood. This study exa mined the effects of prenatal ethanol exposure on the expression of in sulin-like growth factor-1 messenger RNA and type-1 and type-2 recepto r protein and messenger RNA expression in the developing rat brain. Mo thers were maintained on an ethanol containing liquid diet from day 2 of pregnancy through parturition and the offspring were killed at birt h, 10, 20 and 40 days of age. Insulin-like growth factor-1 messenger R NA, and insulin-like growth factor receptors demonstrated developmenta lly dependent expression in specific brain regions throughout the post natal period of CNS maturation. Insulin-like growth factor-1 gene expr ession in the brain, as analysed by dot-blot hybridization, was greate st at birth, and decreased 61% in ad libitum and pair-fed animals by 2 0 days of age. In contrast, ethanol-treated animals exhibited only a 2 5% decrease in insulin-like growth factor-1 messenger RNA levels durin g the same period. This delay in insulin-like growth factor-1 messenge r RNA maturation may be related to a developmental delay in CNS develo pment in the prenatally ethanol exposed offspring. Prenatal ethanol ex posure did not alter the observed localization of insulin-like growth factor-1 messenger RNA. While alterations were observed in long-term i nsulin-like growth factor-1 messenger RNA regulation, quantitative rec eptor autoradiography and in situ hybridization demonstrated no altera tions in either type-1 or type-2 insulin-like growth factor receptor p opulations in ethanol-treated animals. Changes in hepatic and plasma i nsulin-like growth factor-1 and insulin-like growth factor-binding pro tein regulation have also been observed in these animals, suggesting c hanges in protein translation and the autocrine/paracrine actions of t his peptide. The present study demonstrated that insulin-like growth f actor-1 messenger RNA and insulin-like growth factor receptors are reg ionally expressed during early postnatal development and that ethanol administration influenced the long-term regulation of insulin-like gro wth factor messenger RNA levels in the brain without affecting either its localization or insulin-like growth factor receptor populations. T hese results, in combination with previous results from our laboratory on the effects of prenatal ethanol exposure on plasma insulin-like gr owth factor-1 and insulin-like growth factor-binding proteins, provide additional evidence that even modest levels of prenatal ethanol expos ure enhance the possibility of alterations in growth promoting peptide s in the fetus and neonate, leading to an increased risk of fetal alco hol effects in the offspring.