NUTRITIONAL REGULATION OF HORMONES AND GROWTH-FACTORS THAT CONTROL MAMMALIAN GROWTH

Juvenile animals stop growing if they are fed a diet containing an ina dequate amount of energy or protein. The molecular basis for this grow th arrest is not completely understood. The cessation of growth that o ccurs in nutritionally restricted animals is not generally explained b y a decrease in circulating growth hormone (GH). In most species, plas ma GH is increased rather than decreased under conditions of nutrition al restriction. Current evidence suggests that the biosynthesis of ins ulin-like growth factor-I (IGF-I) is a key control point for nutrition al regulation of growth. Plasma IGF-I peptide levels and hepatic IGF-I mRNA abundance are correlated with growth velocity and are consistent ly decreased when growth is arrested by nutritional deprivation. The d ecreased IGF-I mRNA abundance observed in the fasting rat appears to b e caused primarily by a decrease in IGF-I gene transcription. In tissu es and plasma, the insulin-like growth factors are complexed with high -affinity binding proteins, which are thought to modulate the tissue a ccess and action of the IGFs. The hepatic mRNA abundance of two of the binding proteins (IGFBP-1 and -2) is increased in nutritionally restr icted 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 a nd IGF-binding protein gene expression.