Specific binding and effects of dehydroepiandrosterone sulfate (DHEA-S) on skeletal muscle cells: possible implication for DHEA-S replacement therapy in patients with myotonic dystrophy.
Dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) are the most abundant steroidal products and major circulating steroids in humans. The serum concentrations of DHEA-S are lower in patients with myotonic dystrophy (DM) than normal controls, and possible improvement of myotonia and muscle weakness was recently reported following DHEA-S replacement therapy. However, the molecular mechanism of action of DHEA-S remains unknown. To understand the reported anti-DM action of DHEA-S, we investigated DHEA-S binding in skeletal muscle cells in vitro. We identified two populations of DHEA-S binding sites (Kd = 5-9 microM and 35-40 microM) in C2C12 myocytes. Similar binding sites were also identified in human skeletal muscles. The Kd value of the high-affinity site was within the range of serum concentrations of DHEA-S in adult humans. Our results suggest that DHEA-S might act directly on skeletal muscles under normal physiological conditions in humans.
The First Department of Internal Medicine, Osaka Medical College, Takatsuki City, Japan.
K
K
Tsuji
D
D
Furutama
M
M
Tagami
N
N
Ohsawa
D000818:Animals; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism / Q000494:pharmacology; D019314:Dehydroepiandrosterone Sulfate / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D015870:Gene Expression / Q000187:drug effects; D020249:Hormone Replacement Therapy; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D007700:Kinetics; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009223:Myotonic Dystrophy / Q000188:drug therapy*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012995:Solubility; D013256:Steroids / Q000378:metabolism / Q000494:pharmacology; D013347:Subcellular Fractions / Q000378:metabolism
D002788:Cholesterol Esters; D012333:RNA, Messenger; D013256:Steroids; D019314:Dehydroepiandrosterone Sulfate; D007334:Insulin-Like Growth Factor I; C007045:cholesteryl sulfate