Specific binding and effects of dehydroepiandrosterone sulfate (DHEA-S) onskeletal muscle cells: Possible implication for DHEA-S replacement therapyin patients with myotonic dystrophy

Dehydroepiandrosterone (DHEA) and its sulfate (DH EA-S) are the most abunda nt steroidal products and major circulating steroids in humans. The serum c oncentrations of DHEA-S are lower in patients with myotonic dystrophy (DM) than normal controls, and possible improvement of myotonia and muscle weakn ess was recently reported following DHEA-S replacement therapy. However, th e molecular mechanism of action of DHEA-S remains unknown. To understand th e reported anti-DM action of DHEA-S, we investigated DHEA-S binding in skel etal muscle cells in vitro. We identified two populations of DHEA-S binding sites (Kd = 5-9 mu M and 35-40 mu M) in C2C12 myocytes. Similar binding si tes were also identified in human skeletal muscles. The Kd value of the hig h-affinity site was within the range of serum concentrations of DHEA-S in a dult humans. Our results suggest that DHEA-S might act directly on skeletal muscles under normal physiological conditions in humans.