Expression of somatomedin/insulin-like growth factor messenger ribonucleic acids in the human fetus: identification, characterization, and tissue distribution.

Several lines of evidence indicate that multiple human fetal tissues synthesize somatomedins/insulin-like growth factors (Sm/IGFs). To investigate the synthesis of Sm/IGFs in vivo, we isolated polyadenylated RNAs from multiple human fetal tissues of 16-20 weeks gestation and performed Northern and dot-blot analyses using 32P-labeled cDNAs and oligodeoxyribonucleotide (oligomer) probes complementary to human Sm-C/IGF-I and IGF-II mRNAs. Sm-C/IGF-I mRNAs were present in all tissues studied. IGF-II mRNAs were detectable in all tissues except the cerebral cortex and hypothalamus. IGF-II mRNA levels were consistently higher than Sm-C/IGF-I mRNAs in all tissues where IGF-II mRNAs were detectable (varying from 2-fold higher in spleen and thymus to 650-fold higher in liver), suggesting that IGF-II is synthesized in greater quantities than Sm-C/IGF-I in most tissues during early fetal life. Liver, adrenal, and skeletal muscle had the highest levels of IGF-II mRNAs, while placenta and stomach had the highest level of Sm-C/IGF-I mRNAs. Multiple Sm-C/IGF-I and IGF-II transcripts were identified with estimated sizes 0.7, 5.3, and 8.0 kilobases (kb) for Sm-C/IGF-I and 1.8, 2.0, 2.8, 3.0, 4.0, 4.8, and 6.2 kb for IGF-II. The 5.3-kb species was the most abundant Sm-C/IGF-I mRNA. The largest Sm-C/IGF-I transcript (8.0 kb) was identified in the intestine, muscle, kidney, placenta, stomach, heart, skin, pancreas, hypothalamus, and brain stem and was most abundant in the hypothalamus and muscle. The smallest transcript (0.7 kb) was detectable only in spleen, adrenal, placenta, and stomach. On the other hand, nearly all species of IGF-II mRNAs were found in tissues with detectable mRNAs, with the 6.2-kb mRNA being the most abundant. The variation in abundance and species of Sm-C/IGF-I and IGF-II mRNAs among different human fetal tissues suggests tissue-specific differences in Sm-C/IGF-I and IGF-II gene expression, mRNA precursor processing, and/or mRNA stability. Such differences may have significance for the roles of Sm-C/IGF-I and IGF-II during human fetal development. The finding of Sm/IGF mRNAs in many human fetal tissues also supports a local role for Sm/IGFs in human fetal development.