Somatomedin gene structure and expression

Summary

Introduction

The somatomedins or insulin-like growth factors (IGF) are small polypeptides, which play an important role in fetal and postnatal growth and development (Daughaday et al, 1972; Clemmons & Van Wyk, 1981). The somatomedins circulate in plasma and are bound to specific carrier proteins (Hintz, 1984). The liver is known to be the major site of IGF production; in addition, synthesis has been shown to occur in many other tissues (D'Ercole, Applewhite & Underwood, 1980). The primary structure of two major human IGF peptides has been fully established (Rinderkneckt & Humbel, 1978a; Rinderkneckt & Humbel, 1978b).

IGF-I is a basic pep tide of 70 amino acids which is required for growth in postnatal life. For IGF-II, a 67 amino acid neutral peptide, the function is less clear; it may serve an analogous role in fetal development. The nucleotide sequences of complementary DNAs (cDNAs) encoding human IGF-I and IGF-II have been reported (Jansen et al, 1983; Bell et al, 1984; Jansen et al, 1985; Le Bouc et al., 1986; Rotwein, 1986).

From the cDNA characterization it can be deduced that both growth factors are synthesized as larger precursor molecules which undergo extensive processing. Using the cDNAs as specific probes, the chromosomal assignment of the IGF genes has been determined. Both IGFs are encoded by single copy genes; the IGF-I gene maps to the long arm of chromosome 12 and the gene for IGF-II is located on the tip of the short arm of chromosome 11, only 1.4 kilobases (kb) downstream from the insulin gene) Höppener et al, 1985; de Pagter-Holthuizen et al, 1985; Bell et al, 1985; de Pagter-Holthuizen et al, 1987).