Effects of 17α-estradiol treatment strategies on female mice and myogenesis

Purpose: 17α-estradiol (17α-E2), a non-feminizing optical isomer of 17ß-estradiol (17ß-E2), has been shown by The NIA Interventions Testing Program to extend lifespan and improve several characteristics of healthspan in male mice. The purpose of this study was to determine effects of 17α-E2 on female and male muscle cells in vitro and evaluate 17α-E2 treatment strategies in ovariectomized mice. Our hypothesis was that 17α-E2 would increase satellite cell myogenesis and reverse changes in physical activity and body mass expected with ovariectomy (Ovx). Methods: We first identified the optimal dose of 17α-E2 in vitro as 100 pM, and satellite cells from female and male mice were treated daily with 17α-E2, 17ß-E2 or vehicle. Proliferation was measured by MTT and EdU assays 48 or 72 hr later. Ovx C57BL/6J mice were treated with a time release 17α-E2 pellet (IRA), 17α-E2 implant (Belma), 17α-E2 food (TestDiet), 17ß-E2 pellet (IRA), or placebo (n=6 each) for 4 wk. Body mass and food intake were measured intermittently throughout the experiment while physical activity was measured following 4 wk of treatment. Results: Satellite cells isolated from male and female mice responded similarly to 17α-E2 and 17ß-E2 treatment, increasing proliferation compared to vehicle at 48 hr (p=0.008) and 72 hr (p≤0.005). Ovx female mice treated with 17α-E2 food had lower body mass during weeks 2-4 (p<0.001) and less ambulatory distance than mice treated with placebo (p=0.046). Conclusions: Results support our hypothesis that 17α-E2 increases satellite cell proliferation. Ovx mice treated with 17α-E2 in food maintained body mass and cage movement to a greater degree than those treated with other forms of delivery. These results suggest that 17α-E2 may have a beneficial impact on healthspan of estrogen deficient females by improving skeletal muscle maintenance. Supported by NIH R01AG031743, T32AR007612 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.