Insulin-Like Growth Factor I Messenger Ribonucleic Acids with Alternative 5'-Untranslated Regions Are Differentially Expressed during Development of the Rat

Abstract

Solution hybridization/RNase protection assays were used to study the developmental expression of insulin-like growth factor I (IGF-I) mRNA levels in rats. In liver, heart, and kidney, total IGF-I mRNA levels were low at birth and increased during the 50-day postnatal period, with liver levels increasing by over 100-fold. In contrast, stomach, muscle, and testicular IGF-I mRNA levels were highest at the earliest stages examined (late fetal or early neonatal) and declined thereafter to the levels observed in 50-day-old rats. In brain, IGF-I mRNA levels rose 2-fold during the first week of life and declined over the next 6-7 weeks. Lung IGF-I mRNA levels were highest in 20-day-old fetuses and exhibited some fluctuation during the postnatal period. Alternative splicing in the 5''-untranslated region of the primary rat IGF-I transcript gives rise to three transcripts, classes A, B, and C, which have divergent 5''-untranslated region sequences associated with a common region that encodes the mature IGF-I peptide. These sequences contain upstream inframe translation initiation codons and may, therefore, encode alternate IGF-I prepropeptides. The class C variant was the predominant mRNA species at all stages of development studied and was the only IGF-I transcript in brain, heart, and muscle. In tissues where multiple 5''-untranslated region splicing variants occurred, therefore, changes in total IGF-I mRNA primarily reflected changes in this splicing variant. However, the class C and class A (as well as class B in liver) transcripts exhibited temporally divergent changes over some developmental intervals. Class A transcripts in the liver, stomach, testes, and lung as well as class B transcripts in liver, exhibited sustained increases from 15 or 22 postnatal days to maximal levels at 50 postnatal days. In kidney, class A transcripts also increased steadily, but beginning at an earlier stage, i.e. at 8-15 days of postnatal life. These results demonstrate that the temporal expression of total IGF-I mRNA in the developing rat occurs in a tissue-specific manner, and additionally, that IGF-I mRNA variants are differentially expressed during development.