Estradiol and tamoxifen reverse ovariectomy-induced physical inactivity in mice.
Decreased physical activity and increased body mass are associated with estrogen deficiency.


OBJECTIVE
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.


CONCLUSIONS
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.
Gorzek
Jeffrey F
JF
Program in Physical Therapy, University of Minnesota, Minneapolis, MN, USA.
Hendrickson
Kaysie C
KC
Forstner
Jeffrey P
JP
Rixen
Jennifer L
JL
Moran
Amy L
AL
Lowe
Dawn A
DA
D000818:Animals; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D020249:Hormone Replacement Therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D010052:Ovariectomy / Q000009:adverse effects*; D010805:Physical Conditioning, Animal; D013629:Tamoxifen / Q000494:pharmacology*
D013629:Tamoxifen; D004958:Estradiol