Distribution and Regulation of Rat Insulin-Like Growth Factor I Messenger Ribonucleic Acids Encoding Alternative Carboxyterminal E-Peptides: Evidence for Differential Processing and Regulation in Liver

Alternative splicing of insulin-like growth factor I (IGF-l)/somatomedin C mRNAs generates two IGF-I mRNAs coding for IGF-I peptides with different sequences in the E domain of the IGF-I prohormone. These two mRNAs encode alternative E peptides due to the presence (IGF-lb) or absence (IGF-la) of a 52-base insert in the region coding for the E domain. We have used a solution hybridization/RNase protection assay to determine the tissue distribution and regulation by GH of the expression of these alternative IGF-I mRNAs. IGF-lb mRNAs are present in low abundance (representing ~2-5% of the total IGF-I mRNA) in heart, lung, muscle, testes, stomach, kidney, and brain, but represent approximately 13% of the IGF-I mRNA in liver. GH treatment of hypophysectomized rats increased steady-state IGF-I mRNA levels in liver, kidney, lung, and heart. In kidney, lung, and heart, IGF-la and IGF-lb mRNA levels were coordinately regulated by GH, but, in liver, the fold increase in IGF-lb mRNA levels was approximately three times greater than the fold increase in IGF-la mRNA levels. These data suggest that the processing of IGF-I mRNA in liver is different than in nonhepatic tissues. These results also further elucidate the organization of the rat IGF-I gene as well as the generation of multiple IGF-I mRNAs by alternative splicing.