IGFS and Muscle Differentiation

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Abstract

We have studied the stimulation of differentiation by the IGFs for more than a decade, and have now reached a reasonably comprehensive view of this important action of these major hormones. Our recent work makes it clear that a primary mechanism involves increased expression of one of the recently discovered myogenesis genes, myogenin (Florini et al., 1991a). Research on the control of muscle differentiation has been significantly advanced by the discovery of MyoD and three closely related genes, which have been shown to be capable of converting non-muscle cells to the myogenic line, and which are normally expressed only in skeletal muscle cells or their precursors. Myogenin is the member of the family most closely correlated with terminal differentiation, which involves the fusion of myoblasts to form postmitotic myotubes and the concomitant expression of some 20 muscle-specific genes. The IGFs control this process even when they are not added to myoblasts, as incubation of these cells in low-serum medium (the technique most often used to induce differentiation) induces the expression of IGF-II, which then gives autocrine stimulation of myogenesis (Florini et al., 1991b). Indeed, one cell line (Sol 8) secretes so much IGF-II into the medium that we have often found relatively little effect of exogenous IGFs on these cells. The essential role of myogenin in IGF-induced myogenesis, and of autocrine IGF-II in the absence of exogenous IGFs, have been demonstrated by the use of antisense oligodeoxynucleotides complementary to portions of their mRNAs (Florini etal., 1991a, 1991b).