Figure 2.

Selective androgen receptor modulator (SARM), GTx-026, increases muscle mass and strength in mdx mice. (A). GTx-026 is a potent activator of the androgen receptor (AR). AR transactivation studies were performed in HEK-293 cells (left panel) or C2C12 cells (right panel) by transfecting 25 ng CMV-hAR, 0.25 μg GRE-LUC and 10 or 20 ng CMV-renilla-LUC. Twenty-four hours after transfection, cells were treated with vehicle, R1881 or three SARMs (left panel) or GTx-026 (right panel). Cells were harvested 48 h after transfection and luciferase assay was performed. (B) GTx-026 increases muscle mass and strength in mdx mice. Male mdx mice (4 weeks of age; n = 6/group) were castrated to reduce the circulating androgens and treated with vehicle or 10 mg/kg/day s.c. of GTx-026. Weekly body weight and MRI to measure the muscle mass were recorded. Grip strength was measured at the start of the experiment, and after 6 and 12 weeks. Values are represented as percent change from baseline. *P < 0.001 (body weight and muscle mass) and P < 0.05 (grip strength). (C) GTx-026 improves prednisolone effects on body weight and muscle mass in castrated mdx mice. Castrated mdx mice (n = 5/group) were treated with vehicle, prednisolone (5 mg/kg/day p.o.) or GTx-026 (10 mg/kg/day s.c.) or combination of prednisolone and GTx-026 for 6 weeks. Body weight, body composition and grip strength were measured at the beginning of the study and at weeks 3 and 6. *P < 0.01. (D) Clinically comparable doses of GTx-026 improve body weight and lean mass in mdx mice. Castrated mdx mice (n = 6/group) were treated orally with vehicle or indicated doses of GTx-026. Body weight and composition were measured at the beginning of the study and after 3, 6 and 9 weeks of dosing. *P < 0.001. RLU, relative light units; mpk, milligrams per kilogram.