INDUCTION OF GENE-EXPRESSION IN MUSCLE BY THE IGFS

The insulin-like growth factors (IGFs) are usually studied with regard to their general effects on cell growth or differentiation, but the latter actions imply that IGFs may also have effects on expression of specific genes in differentiating target tissues. After 15 years of studies on IGF actions on muscle, we have (with the help of an outstanding group of collaborators) found three specific instances in which IGFs induce expression of a well-characterized gene with at least some degree of specificity. Each of the three genes under consideration plays a major role in the tissue that expresses it, and each of the three kinds of muscle is represented. The genes are (1) skeletal muscle myogenin, which plays a central role in terminal myogenic differentiation of muscle cells to form postmitotic myotubes, (2) smooth muscle aortic elastin, which is of major importance in regulation of blood pressure, and (3) cardiac beta-myosin heavy chain, which is the primary component of the contractile apparatus in older rodents and in all humans. For the first two of these, it has been established that the stimulation is largely if not completely at the level of increased mRNA synthesis, and that reporter gene constructs using 5-untranslated regions of the gene exhibit analogous responses to IGFs, offering the possibility that consensus IGF response elements can be elucidated. The importance of IGFs for skeletal myogenic differentiation is underscored by the observation that myoblasts in 'differentiation' medium exhibit substantial expression of IGF-II if IGFs are not added to the medium. Thus the IGFs play major roles in functions of all three kinds of muscle. The potential medical significance of these actions of the IGFs add further interest to a recent report 1 on beneficial effects of GH administration to elderly patients.