Nutritional regulation of hormones and growth factors that control mammalian growth

Juvenile animals stop growing if they are fed a diet containing an inadequate amount of energy or protein. The molecular basis for this growth arrest is not completely understood. The cessation of growth that occurs in nutritionally restricted animals is not generally explained by a decrease in circulating growth hormone (GH). In most species, plasma GH is increased rather than decreased under conditions of nutritional restriction. Current evidence suggests that the biosynthesis of insulin-like growth factor-I (IGF-I) is a key control point for nutritional regulation of growth. Plasma IGF-I peptide levels and hepatic IGF-I mRNA abundance are correlated with growth velocity and are consistently decreased when growth is arrested by nutritional deprivation. The decreased IGF-I mRNA abundance observed in the fasting rat appears to be caused primarily by a decrease in IGF-I gene transcription. In tissues and plasma, the insulin-like growth factors are complexed with high-affinity binding proteins, which are thought to modulate the tissue access and action of the IGFs. The hepatic mRNA abundance of two of the binding proteins (IGFBP-1 and -2) is increased in nutritionally restricted animals. This increase in mRNA abundance is caused primarily by an increase in transcription of the IGFBP-1 and IGFBP-2 genes. Current research is focused on molecular mechanisms for regulation of IGF-I and IGF-binding protein gene expression.