Growth Hormone and the Insulin-Like Growth Factor System in Myogenesis*

THE general characterization of the growth hormone/insulin-like growth factor-I (GH/IGF-I) system has been established for a considerable length of time, and we will not repeat the many detailed descriptions of these proteins. Specifics of GH structure and general actions are presented in reviews such as those by Li (1) and by Laron (2). A later review (3) summarizes much of the early literature on biological effects of GH, with some emphasis on effects on isolated muscles. Carter-Su et al. (4, 5) have summarized more recent findings on the mechanisms of GH interactions with its receptor and subsequent intracellular signals; virtually all of this has been done in nonmuscle systems. The induction of hepatic IGF gene expression by GH has been well established for a long time, and we will not cover this area here, as we are concerned with actions of the IGFs rather than their secretion by liver. Information on the structures of the IGFs and their binding proteins, as well as their actions in nonmuscle systems, is presented in a number of recent comprehensive reviews (6–19). For this review, we simply specify that GH is a simple protein (containing only one intrachain S-S bond, and relatively unstable) of 22 kDa, and the IGFs (IGF-I and IGF-II) are single chains with three intrachain disulfides (and quite high stability in neutral or acid conditions) of about 7.5 kDa. In addition, six IGF-specific binding proteins (IGFBP-1 to -6) have been characterized. The IGFBPs include numerous disulfides and are remarkably stable, retaining substantial IGF-binding activity after precipitation with trichloroacetic acid and separation by SDS gel electrophoresis (10). A cartoon summarizing a current view of the GH/IGF system is presented in Fig. 1.