Testosterone Stimulates Intracellular Calcium Release and Mitogen-Activated Protein Kinases Via a G Protein- Coupled Receptor in Skeletal Muscle Cells

Involvement of intracellular Ca2+ and ERK1/2 phosphorylation in the fast nongenomic effects of androgens in myotubes was investigated. Testosterone or nandrolone produced fast (<1 min) and transient increases in intracellular Ca2+ with an oscillatory pattern. Calcium signals were slightly reduced in Ca2+-free medium, but lack of oscillations was evident. Signals were blocked by U-73122 and xestospongin B, inhibitors of inositol 1,4,5-trisphosphate (IP3) pathway. Furthermore, IP3 increased transiently 2- to 3-fold 45 sec after hormone addition. Cyproterone neither affected the fast Ca2+ signal nor the increase in IP3. Calcium increases could also be induced by the impermeant testosterone conjugated to BSA, and the effect of testosterone was abolished in cells incubated with guanosine 5′-O-(2-thiodiphosphate) or pertussis toxin. Stimulation of myotubes with testosterone, nandrolone, or testosterone conjugated to BSA increased immunodetectable phosphorylation of ERK1/2 within 5 min, and this effect was not i...