Estradiol and Tamoxifen Reverse Ovariectomy-Induced Physical Inactivity in Mice

Gorzek JF, Hendrickson KC, Forstner JP, Rixen JL, Moran AL, Lowe DA.

Medicine and Science in Sports and Exercise 2007

                Physical activity is crucial to maintaining a positive health and it has been shown that there are many positive adaptations in multiple different systems that can come from regular physical activity. These systems can include the cardiovascular system, immune system, musculature system and probably the nervous system as well. Many studies have shown that female rats consistently run more than their male counterparts. Furthermore, it has been shown that this difference in running is most likely due to the presence of female hormones produced in the ovaries. Something interesting to me is why are the females running more than the males. If it is the ovarian hormones, what are they doing to cause the female to run more? Is it affecting their motivation to run or their physical ability to run? And if it is the physical ability to run, is it in the nervous system of in the skeletal and musculature system? The purpose of this study was to assess the effect that ovariectomy and then estrogen replacement or tamoxifen replacement had on voluntary physical activity as well as body mass.

                There were two studies conducted in this paper. In the first study mice were assigned to either sham group, ovariectomy with estrogen group, or ovariectomy with placebo group. At week four (14 weeks old) surgeries were performed which were either bilateral ovariectomy or sham surgery. After the surgery and then a week recovery period mice were given access to a wheel to run on. Mice ran for 4 weeks before either estradiol or placebo replacement took place. Subcutaneous pellets of estradiol or placebo were placed under the skin of the mice and then the mice were allowed to run for another 4 weeks at which point they were sacrificed.

                In the second study, all mice were ovariectomized and then placed in one of three groups: estradiol replacement, tamoxifen replacement or placebo replacement. In this study surgeries were performed at the same time as the pellet placement and then the mice were given 3 days to recover and then put in their cages with wheels. At this point mice were allowed to run for 6 weeks and then sacrificed.

                All mice were kept on 12:12 light dark cycle. Surgeries were performed under anesthesia. Wheel running was assessed by mean weekly measures of distance.

                As expected, in the first study, the group of ovariectomy mice ran significantly less than the control sham group. The ovariectomy with estradiol group ran more similar to the placebo group until the replacement period at which point they increased their running significantly and ran more alike to the control group.  In the second study the data shows that all three groups increased their running as they acclimated to the wheel in the pre-surgery time frame. Once surgeries were performed the running of the placebo group declined significantly from before the surgery. The groups that were immediately treated with tamoxifen or estradiol maintained their running behavior more steadily, although there was some decline over time. The treatment groups with tamoxifen and estradiol ran significantly more than the placebo group, but the two treatment groups were not significant from one another.
                This study indicates that the decrease seen in physical activity in females after loss of ovarian hormones is indeed due to the loss of those ovarian hormones. Due to the use of tamoxifen in this study, it was also indicated that this hormone dependent change in running behavior is mediated by the estrogen receptor. The study also suggests that do to their measurements in body weight, hind limb weight, and heart muscle weight, it was more likely that the estrogenic compounds caused the mice to have more motivation to run rather than causing changes in their musculoskeletal system that allowed them to run more. Still to be uncovered is whether or not estrogenic compounds could cause differences In the brain that that provide the nutrition and blood for more exercise to occur – aka RVLM.

Ben R