Molecular Biology of the Somatomedins

Abstract

The insulin-like growth factors (IGF-I and IGF-II) are growth-promoting peptides which are structurally related to insulin and, to a lesser extent, relaxin (Blundell et al. 1983). As shown in Fig. 1, the IGF-I and IGF-II precursor peptides are similar to insulin in that they contain B and A domains which are homologous to the B and A chains of insulin, and which are separated by a C domain which, in contrast to the C peptide of insulin, is not removed during prohormone processing. Signal peptide sequences precede the mature peptide sequence of all of these secreted molecules. Unlike insulin, the mature IGF-I and II peptides contain, in addition to the B, C, and A domains, a C-terminal D domain for which no analogy exists in insulin. Finally, the IGF prohormones contain carboxy terminal E peptides which are usually cleaved post-translationally. The initial role of IGF-I was proposed to be the mediation of the effects of GH on longitudinal bone growth (Salmon and Daughaday 1957). Subsequently, the discovery of IGF-I peptide (D’Ercole et al. 1984) and mRNA (Lund et al. 1986) in multiple tissues has expanded the original “somatomedin hypothesis” to encompass local autocrine and/or paracrine actions of IGF-I. IGF-II, originally characterized as “multiplication-stimulating activity,” or MSA (Dulak and Temin 1973), is generally found at higher concentrations during prenatal stages of development, so that it has generally been considered to be a fetal growth factor, with IGF-I contributing more to post-natal growth.