Tissue and Development Specific Regulation of a Complex Family of Rat Insulin-Like Growth Factor I Messenger Ribonucleic Acids

Abstract

To obtain information about the functional significance of the structural heterogeneity that has been described for rat insulin-like growth factor I (IGF-I) cDNAs, we hybridized polyadenylated RNAs from rat tissues at different developmental stages with probes specific for two variant 5'-sequences (designated here as type 1 and type 2), with a probe specific for IB type E domain coding sequences and with a probe for E domain sequences common to IA and IB type IGF-I cDNAs. Northern blot analyses revealed that previously reported rat liver IGF-I mRNAs of estimated size 7.5-7.0, 1.9-1.5, and 1.2-0.9 kilobases each are comprised of multiple closely migrating IGF-I mRNA species containing either of two 5'-sequences and either IA or IB type E domain coding sequences. In liver, each of these detected IGF-I mRNA species showed postnatal increases in abundance. The mRNAs detected with the probe for type 2 5'-sequences were detected exclusively in postnatal liver and also showed a different pattern of postnatal increase in abundance than other IGF-I mRNA types. IGF-I mRNAs detected with the probe for IB type E domain coding sequences likewise were highly liver specific and were undetectable or barely detectable in other fetal or adult rat tissues. In contrast, IGF-I mRNAs that hybridized with probes for type 1 5'-sequences or for E domain coding sequences common to IA and IB type IGF-I mRNAs were detected in all fetal and adult rat tissues tested. These findings suggest development and tissue specific regulation of the expression of different rat IGF-I mRNA types, and also suggest a possible role of different precursor sequences encoded by the various mRNAs in targeting of IGF-I to a local site of action.

Sequestration and secretion of insulin‐like growth factor‐I by bovine aortic endothelial cells

“…Delafontaine et al (1991) found 2.1-kb and 1.6-kb IGF-I mRNA transcripts in endothelium by northern analysis and concluded that endothelial cells both synthesized and secreted IGF-I. In this report, the IGF-I mRNA transcript observed in endothelial cells was a 7.5-7.0 kb form, identical to that demonstrated in adult porcine and bovine liver, and in other tissues from other species (Hoyt et al, 1988;Lund et al, 1986). In comparison, Sarazani et al (1989) detected a major 7.8-kb IGF-I mRNA in rat aortic tissue and Lund et al (1986) noted that the predominant IGF-I mRNA transcript in nonhepatic tissue was a 7.5-to 7.0-kb form.…”

Normal growth and development in the absence of hepatic insulin-like growth factor I

“…Serum concentrations of IGF-I are low in the fetal and early postnatal periods compared with adult levels, increasing markedly during puberty (1). It is believed that the adult liver, which exhibits a several order of magnitude higher level of postnatal igf1 gene expression than any other tissue, is the source for circulating IGF-I (22)(23)(24)(25). Sera of 6-week-old mice were examined for the presence of immunoreactive IGF-I ( Table 1).…”

Organ-Specific and Age-Dependent Expression of Insulin-like Growth Factor-I (IGF-I) mRNA Variants: IGF-IA and IB mRNAs in the Mouse

“…In the rat liver, transcription initiation at exon 2 was reduced in diabetes and fasting. Class 1 transcripts are ubiquitous and predominant in all tissues, and Class 2 transcripts are detected in liver (Hoyt et al, 1988). O'Sullivan et al (2002) studied regulation of class 1 and class 2-IGF-I mRNAs in lamb liver, and showed that GH may stabilize mature class 2-IGF-I mRNA or destabilize mature class 1-IGF-I mRNA and the class 2-IGF-I mRNA may have a greater overall translational potential.…”