Estradiol and Tamoxifen Reverse Ovariectomy-Induced Physical Inactivity in Mice

UNLABELLED: Decreased physical activity and increased body mass are associated with estrogen deficiency. PURPOSE: To determine whether estrogen or the estrogen analog, tamoxifen, could reverse those detrimental effects after surgical ovariectomy in mice. METHODS: Ten-week-old C57BL/6 mice were sham operated (sham, N = 6) or ovariectomized (OVX, N = 9). After 4 wk of voluntary wheel running, placebo (OVX-P) or 17beta-estradiol (OVX-E2) pellets were implanted and the mice ran an additional 4 wk. A second study followed in which mice received placebo, 17beta-estradiol, or tamoxifen (OVX-Tam) simultaneously with ovariectomies. Distances run per 24 h and body masses were analyzed by two-way ANOVA with repeated measures. RESULTS: During the initial 4 wk, OVX mice ran approximately 80% less and had approximately 20% greater body masses compared with sham mice (P < 0.001). Estradiol replacement quickly reversed the inactivity as OVX-E2 mice increased their running from 1.9 +/- 0.3 km x 24 h(-1) to 6.9 +/- 0.7 km within a week of replacement, which was equivalent to shams (8.1 +/- 0.7 km), whereas OVX-P mice ran only 0.5 +/- 0.2 km (P < 0.01). OVX-E2 mice tended to maintain body mass after estradiol replacement, whereas the OVX-P mice continued to increase mass. OVX mice that received tamoxifen had high running activity, approximately 9 km x 24 h(-1), and maintained body mass. CONCLUSION: The removal of ovarian hormones caused mice to become inactive and gain body mass. Hormone therapy in the form of 17beta-estradiol or tamoxifen rapidly stimulated voluntary wheel running and reversed body mass gains, indicating that estrogen receptor binding was involved in regulating physical activity.