Hormones, growth factors, and myogenic differentiation.

Three families of growth factors/hormones have major effects on the differentiation of skeletal muscle cells. Two (FGF and TGF-beta) are potent inhibitors, and the third (IGF) exhibits a biphasic stimulatory action (but is not inhibitory even at high concentrations). All of these affect the expression of myogenin, one of the recently discovered family of myogenesis controlling genes, and FGF and TGF-beta have been shown to inhibit the expression of MyoD1 (and probably myf-5 and herculin) as well. These agents inhibit or stimulate (respectively) all measured aspects of myogenic differentiation--fusion, expression of a set of muscle-specific genes, and attainment of a postmitotic state--in all cells that are capable of these responses, whether cell lines or primary muscle cell cultures. It now seems clear that the myogenesis controlling genes regulate the entire family of muscle-specific proteins. Therefore the demonstration that expression of these genes is controlled (both positively and negatively) by specific growth factors that are now available at high purity and in useful quantities offers the possibility of understanding myogenic differentiation at a level of molecular detail that is very exciting.