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-I)/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-Ib) or absence (IGF-Ia) 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-Ib mRNAs are present in low abundance (representing approximately 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-Ia and IGF-Ib mRNA levels were coordinately regulated by GH, but, in liver, the fold increase in IGF-Ib mRNA levels was approximately three times greater than the fold increase in IGF-Ia 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.
Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892.
W L
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Lowe
S R
SR
Lasky
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D
LeRoith
C T
CT
Roberts
D000818:Animals; D005786:Gene Expression Regulation; D013006:Growth Hormone / Q000494:pharmacology; D007016:Hypophysectomy; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D008297:Male; D009693:Nucleic Acid Hybridization; D010446:Peptide Fragments / Q000235:genetics*; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012260:Ribonucleases; D012996:Solutions; D013002:Somatomedins / Q000235:genetics*; D014018:Tissue Distribution
D010446:Peptide Fragments; D012333:RNA, Messenger; D012996:Solutions; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D012260:Ribonucleases