The IGF system during growth and differentiation of the mouse

The insulin-like growth factors (IGFs) were first discovered in 1957 by Salmon and Daughaday (1957). They found that in vivo administration of growth hormone (GH) induced a serum factor capable of stimulating sulfate uptake in cartilage. In 1972 this 'sulfation factor' was renamed somatomedin (mediator of the effects of somatotropin, GH) and classified as a growth factor (Daughaday et aI., 1972). At the same time, a compound named NSILA (nonsuppressible insulin-like activity) was found (Froesch et aI., 1966). NSILA and somatomedin each stimulated glucose incorporation into fat and sulfate incorporation into cartilage (Froesch et aI., 1976). The amino acid sequence of NSILA showed 48% homology with human pro-insulin. Therefore it was called insulin-like growth factor-I (IGF-I) (Rinderknecht and Humbel, 1978a). A second bioactive insulin-like molecule appeared to be similar, but not identical, and was named IGF-II (Rinderknecht and Humbel, 1978b). Somatomedin appeared to be identical to IGF-I (Svoboda et aI., 1980). Now, over forty years later, in vivo studies, gene expression experiments, and determination of signalling pathways have provided more insight into IGF actions. IGF receptors and IGF binding proteins (IGFBPs) have been characterized (Chernausek et aI., 1981; Kasuga et aI., 1981; Brinkman et aI., 1988; Binkert et aI., 1989; Margot et aI., 1989; Shimasaki, 1989; Murphy et aI., 1990; Shimasaki, 1990; 1991a/b; Schuller et aI., 1994). This, and the recent discovery of IGFBP related proteins, have shown the complexity of the IGF system (Oh et aI., 1996). It is clear that the IGFs, together with the other IGF system compounds, playa pivotal role in body and organ development and growth. Therefore, this chapter will review in more detait characteristics of the separate components of the IGF system. Then, focus is put on the IGF system during mouse development. A summary of the data generated to elucidate the functions of the IGF system during mouse development is described.