Estrogen Receptor Alpha (ERα) Is Involved in Resveratrol-Mediated Muscle Preservation During Mechanical Unloading in Male Rats

NASA intends to return humans to the Moon, where partial gravity will put them at risk of musculoskeletal deconditioning. Resveratrol (RSV) is a promising nutritional countermeasure that may protect muscle health during disuse; however, its efficacy and mechanism in simulated lunar gravity are unknown. Forty adult male Wistar rats underwent 14 days of normal loading or partial weight-bearing at 20% of normal loading (PWB20). Unloaded animals received daily RSV supplementation with or without an ERα antagonist to test whether ERα was required to mediate RSV benefits. Muscle function was longitudinally assessed, and a Western blot was used to quantify key signaling proteins in the soleus muscle. PWB20 led to a significant reduction in grip strength (−14.2%) associated with marked changes in electrophysiological muscle properties. RSV-supplemented animals performed better throughout the study, but not when Erα was inhibited. RSV supplementation resulted in a greater ERα phosphorylation ratio compared to PWB20 alone (3.5 vs. 1.91). These results suggest that RSV can mitigate muscle deconditioning in a lunar gravity analog and that ERα signaling is required.