GLUCOCORTICOID EFFECTS ON THE SKELETAL-MUSCLE DIFFERENTIATION PROGRAM- ANALYSIS OF CLONAL PROLIFERATION, MORPHOLOGICAL-DIFFERENTIATION ANDTHE EXPRESSION OF MUSCLE-SPECIFIC AND REGULATORY GENES

We examined the effect of glucocorticoids on the proliferation and dif ferentiation of skeletal muscle cells using the C2C12 cell line. We fo und that treatment with glucocorticoids enhanced muscle cell different iation but had only minor effects on the clonal growth rate of C2C12 c ells. The stimulatory effect of glucocorticoids on myogenic differenti ation was reflected in the; increased expression of muscle-specific ge nes, creatine kinase (CK) and acetylcholine receptor gamma subunit (AC hR). Dexamethasone had no effect on CK and AChR mRNA stability and enh anced transcription from a CAT reporter genes containing the 3.3kb 5' flanking region of the murine CK gene (-3300MCK-CAT). Since dexamethas one did not affect the expression levels of the myogenic regulatory ge nes such as myoD and myogenin, the enhancement of muscle-specific tran scription might reflect an increase in the functional activity of-the regulatory proteins. Other possible mechanisms involved in the differe ntiation-enhancing effect of glucocorticoids are discussed.