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

• Published in: Life sciences (1973) Vol. 65; no. 1; pp. 17 - 26
• Main Authors: Tsuji, Kuniko, Furutama, Daisuke, Tagami, Muneyoshi, Ohsawa, Nakaaki
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 1999
• Subjects: Animals; Binding, Competitive; C2C12 cells; Cell Division - drug effects; Cell Line; Cell Nucleus - metabolism; Cholesterol Esters - metabolism; Cholesterol Esters - pharmacology; Dehydroepiandrosterone Sulfate - antagonists & inhibitors; Dehydroepiandrosterone Sulfate - metabolism; Dehydroepiandrosterone Sulfate - pharmacology; Dehydroepiandrosterone Sulfate - therapeutic use; DHEA-S; Gene Expression - drug effects; Hormone Replacement Therapy; Humans; IGF-I; Insulin-Like Growth Factor I - genetics; Kinetics; Mice; Muscle, Skeletal - cytology; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Myotonic Dystrophy - drug therapy; RNA, Messenger - genetics; RNA, Messenger - metabolism; Scatchard analysis; Solubility; Steroids - metabolism; Steroids - pharmacology; Subcellular Fractions - metabolism; Scatchard analysis; IGF-I; C2C12 cells; DHEA-S
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/S0024-3205(99)00215-5

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 μM and 35–40 μM) 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.