Pii: S0960-8966(02)00089-5

Previous studies on transgenic mice indicate that upregulation of utrophin protein may offer a potential treatment strategy for Duchenne muscular dystrophy. We have analyzed the effect of the glucocorticoid 6a-methylprednisolone-21 sodium succinate on utrophin protein levels using a cell-based assay with differentiated human myotubes derived from biopsies of healthy individuals or Duchenne muscular dystrophy patients. We found that within 5–7 days 6a-methylprednisolone-21 sodium succinate increases utrophin protein up to ,40% in both normal and dystrophin-deficient myotubes compared to untreated control cultures. When analyzed in promoter–reporter assays 6amethylprednisolone-21 sodium succinate activated a utrophin promoter A-fragment but did not activate a utrophin promoter B-fragment. Surprisingly, endogenous levels of utrophin mRNA in 6a-methylprednisolone-21 sodium succinate-treated muscle cells were unaltered indicating that the utrophin-inducing effect of glucocorticoids may be a result of post-transcriptional mechanisms. We have also analyzed 66 glucocorticoids for their effect on utrophin protein levels and found that glucocorticoids in general are able to induce utrophin protein in human myotubes. q 2002 Published by Elsevier Science B.V.