Nutritional regulation of the genes encoding the acid-labile subunit and other components of the circulating insulin-like growth factor system in the sheep.

In sheep, perinatal maturation of the endocrine arm of the insulin-like growth factor (IGF) system is characterized by two developmental events. First, concentrations of circulating IGF-I increase rapidly after birth and become responsive to changes in nutrition and growth hormone (GH). Second, the liver initiates synthesis of a serum protein called the acidlabile subunit (ALS). The acid-labile subunit promotes the endocrine actions of IGF-I and -II by recruiting them to long-lived complexes of 150 kDa. In this study, we examined the effect of nutrition on hepatic expression of the ALS gene around the time of birth and later in life. Expression of genes encoding other components of the circulating IGF system was also measured. At d 130 of fetal life, fetuses suffering from chronic undernutrition caused by placental insufficiency had lower expression of the ALS and IGF-I genes than well-nourished fetuses, but they did not have any changes in the expression of the IGF-binding protein (IGFBP)-2 or IGFBP-3 genes. In early postnatal life, hepatic gene expression was analyzed between d 12 and 38 in lambs fed a milk replacer at levels sustaining weight gains of 150 or 337 g/d. The lower plane of nutrition decreased the expression of the ALS, IGF-I, and GH receptor genes and increased the expression of the IGFBP-2 gene; expression of the IGFBP-3 gene was not affected by nutrition at this stage of life. Finally, hepatic gene expression was measured in 3-mo-old lambs offered ad libitum levels of a balanced diet or of a diet limiting for both energy and protein. Although the rate of growth of the lambs fed the limiting diet was reduced by 38%, the only effect detected in hepatic gene expression was a ninefold increase in the abundance of IGFBP-2 mRNA. Overall, these results indicate that undernutrition during late fetal and early postnatal life delays hepatic expression of the ALS gene and final maturation of the endocrine IGF system.