Glucocorticoid inhibition of C2C12 proliferation rate and differentiation capacity in relation to mRNA levels of the MRF gene family

The muscle regulatory factors (MRF) gene family regulate muscle fibre devel opment. Several hormones and drugs also affect muscle development. Glucocor ticoids are the only drugs reported to have a beneficial effect on muscle d egenerative disorders. We investigated the glucocorticoid-related effects o n C2C12 myoblast proliferation rate, morphological differentiation, and sub sequent mRNA expression patterns of the MRF genes. C2C12 cells were incubat ed with the glucocorticoids dexamethasone or alpha-methyl-prednisolone. Bot h glucocorticoids showed comparable effects. Glucocorticoid treatment of C2 C12 cells during the proliferative phase reduced the proliferation rate of the cells dose dependently, especially during the third and fourth day of c ulture, increased MyoD1, myf-5, and MRF4 mRNA levels, and reduced myogenin mRNA level, compared to untreated control cells. Thus, the mRNA level of pr oliferation-specific MyoD1 and myf-5 expression does not seem to associate with C2C12 myoblast proliferation rate. Glucocorticoid treatment of C2C12 c ells during differentiation reduced the differentiation capacity dose depen dently, which is accompanied by a dose dependent reduction of myogenin mRNA level, and increased MyoD1, myf-5, and MRF4 mRNA levels compared to untrea ted control cells. Therefore, we conclude that glucocorticoid treatment red uces differentiation of C2C12 myoblasts probably through reduction of diffe rentiation-specific myogenin mRNA level, while inducing higher mRNA levels of proliferation-associated MRF genes.