Hormonal induction of an immediate-early gene response in myogenic cell lines--a paradigm for heart growth.

Cardiac hypertrophy is characterized by growth of myocardial cells without proliferation. Many endo- paracrine stimuli such as angiotensin II, endothelin, alpha 1-adrenergic agonists, and insulin have been shown to be able to induce cardiac hypertrophy either in vivo or in vitro. We have used the myoblast model of differentiation and proliferation to determine nuclear signal transduction mechanisms in muscle and (by analogy) cardiac growth. The first nuclear event known to occur when a growth stimulus acts upon a cell is induction of a family of immediate-early genes. Our group focused on the role of one of these genes, the early growth response gene-1 (Egr-1). We have shown that this gene is induced in isolated adult cardiac myocytes in the presence of endothelin. An anti-sense oligonucleotide complementary to the first six codons of the Egr-1 mRNA abolishes the stimulation of protein synthesis induced by endothelin. In the present study we further characterized paracrine growth stimuli in the myogenic cell line Sol8, which was used as a paradigm to further investigate mechanisms of paracrine growth induction. We demonstrated that a variety of candidate endo- paracrine stimuli for the induction of cardiac hypertrophy induced the Egr-1 messenger RNA in the myogenic cell line Sol8. Among these are endothelin, insulin, basic fibroblast growth factor, and platelet-derived growth factor BB (PDGF BB). We conclude: (1) In analogy to the myocardium, these growth factors act upon myoblasts. (2) This line appears to be a suitable model for the molecular characterization of Egr-1 target genes.