Insulin-like growth factor I messenger ribonucleic acids with alternative 5'-untranslated regions are differentially expressed during development of the rat.
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 in-frame 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.
Adamo
M
M
Section of Molecular and Cellular Physiology, Diabetes Branch, National Institute of Diabetes, Bethesda, Maryland 20892.
Lowe
W L
WL
LeRoith
D
D
Roberts
C T
CT
D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D004622:Embryo, Mammalian; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008297:Male; D009693:Nucleic Acid Hybridization; D009928:Organ Specificity; D014176:Protein Biosynthesis; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D011919:Rats, Inbred Strains; D013002:Somatomedins / Q000235:genetics*; D014158:Transcription, Genetic
D012333:RNA, Messenger; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I