Estradiol and Tamoxifen Reverse Ovariectomy-Induced Physical Inactivity in Mice

GORZEK, JEFFREY F.1; HENDRICKSON, KAYSIE C.1; FORSTNER, JEFFREY P.1; RIXEN, JENNIFER L.1; MORAN, AMY L.2; LOWE, DAWN A.1

Medicine & Science in Sports & Exercise: February 2007 - Volume 39 - Issue 2 - pp 248-256
doi: 10.1249/01.mss.0000241649.15006.b8
BASIC SCIENCES: Original Investigations

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 17β-estradiol (OVX-E2) pellets were implanted and the mice ran an additional 4 wk. A second study followed in which mice received placebo, 17β-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·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·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 17β-estradiol or tamoxifen rapidly stimulated voluntary wheel running and reversed body mass gains, indicating that estrogen receptor binding was involved in regulating physical activity.

1Program in Physical Therapy; and 2School of Kinesiology, University of Minnesota, Minneapolis, MN

Address for correspondence: Dawn A. Lowe, MMC 388, 420 Delaware St. SE, Minneapolis, MN 55455; E-mail: lowex017@umn.edu.

Submitted for publication March 2006.

Accepted for publication August 2006.

©2007The American College of Sports Medicine