Clenbuterol mimics effects of innervation on myogenic regulatory factor expression

The amelioration of denervation atrophy by the beta-adrenoceptor agonist clenbuterol has led to the suggestion that the drug mimics or stimulates production of neurotrophic factors. Neurotrophic factors have profound effects on muscle growth, but the precise mechanisms through which this influence is exerted are unknown. The expression of myoD and myogenin, proteins that in turn regulate the transcription of tissue-specific genes during skeletal muscle differentiation, is controlled by innervation. In muscle undergoing denervation-induced atrophy, myoD and myogenin mRNAs increase. However, this is only partially reversed by electrical activity, thus implicating neurotrophic factors in regulation of these genes. Here we demonstrate that clenbuterol represses myoD and myogenin expression and decreases the levels of acetylcholine receptors in denervated muscles. The data provide the first evidence that the action of clenbuterol is directed through the neural axis.