life prolonging function, IGFBPs may inhibit or enhance the activity if IGF-I [59, 60, 61].

They may also target IGFs to specific cells. IGFBPs are not only present in serum but are

also produced locally by many different cells where they may have important functions in

binding and/or targeting IGF-1 to the respective receptors [62, 63]. The IGFBPs differ in

their regulation and their affinities for IGF-1 [62, 63]. In addition to carrier proteins,

there is increasing evidence that they act as potentiators or modulators of several complex

physiological activities of IGF-1 [64].

 The biologic activities of IGF-1 can be divided into two types of responses: rapid

metabolic effects (insulin-like), and slower growth-promoting effects (mitogenic) [64,

65]. It has been demonstrated that these peptides act as mitogens for many cell types [66,

67]. In this capacity, IGF-1 appears to allow the cell to progress from GI to S phase of

the cell cycle. In fibroblasts, other factors such as PDGF or EGF are required to make

the cell component to traverse the cell cycle [68, 69]. Thus, PDGF, EGF, FGF and other

factors may act to render cells competent for the action of IGF-1, which was termed

progression factors. Muscle cells, chondrocytes, and osteoblasts grow rather well in the

absence of any other growth factors when stimulated by IGF-1 [70], and, in semi viscous

medium form colonies of highly differentiated cells [71, 72]. Osteoblasts increase type I

procollagen messenger RNA levels under the influence of IGF-1 [73]. IGF-1 also

stimulates the degree of differentiation of osteoblasts in newborn rats [74] and of primary

embryonic chick muscle cells [70]. IGF-1 stimulates myofibril development in adult rat

cardiomyocytes in vitro [75]. IGF-1 administered in vivo to hypoxic rats has the same

effects as GH on chondrocyte differentiation in the epiphysis [76].