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 | Zendy

William L. Lowe | Zendy; Stephen R. Lasky | Zendy; Derek LeRoith | Zendy; Charles T. Roberts | Zendy

Open Access

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

Author(s) -

William L. Lowe,

Stephen R. Lasky,

Derek LeRoith,

Charles T. Roberts

Publication year - 1988

Publication title -

molecular endocrinology

Language(s) - English

Resource type - Journals

eISSN - 1944-9917

pISSN - 0888-8809

DOI - 10.1210/mend-2-6-528

Subject(s) - biology , messenger rna , somatomedin , alternative splicing , prohormone , primary transcript , growth factor , insulin like growth factor , kidney , gene expression , insulin like growth factor 2 , endocrinology , medicine , microbiology and biotechnology , receptor , gene , biochemistry , hormone

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.

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