Loss of Sex Steroids Affects Wheel Running Patterns in Male and Female Mice
Authors: Lombard Clara E. , Loy Ethan E. , Bowen Robert S. 
Published: April 2020

Physical inactivity increases chronic disease risk and can lead to premature death. Aging can lead to changes in sex steroid levels that might influence physical activity patterns leading to the higher risk for hypokinetic diseases. The purpose of this study is to evaluate changes in wheel running patterns in response to changing sex steroid levels in male and female C57BL/6J mice. Male and female mice (n = 20) were acquired at eight weeks of age. All mice were housed individually with access to running wheels that were monitored on a turn‐by‐turn basis. Mice acclimated to the cage environment and running wheels for ten days before data collection began. At the end of acclimation, all mice underwent surgical (n = 8) or sham (n = 10) gonadectomies to induce hormone deficiency; two surgically treated mice were euthanized immediately following surgery due to complications during recovery. Wheel running data were collected for seven days and each wheel revolution was counted and time‐stamped to accumulate a daily turn‐by‐turn wheel revolution record. Daily wheel running records were used to calculate 24‐hour averages across the seven day experimental period for distance (km), duration (min), and speed (m·min−1). Instantaneous rotational speed was calculated for each wheel rotation. The average frequency of instantaneous speed (percentage of all rotations) was collected across five speed ranges (0–15, 15–25, 25–35, 35–45, 45 or more m·min1). Two‐way ANOVAs were used to evaluate differences in 24‐hour distance, duration, and speed in relation to hormone status (hormone‐deficient vs. normal hormone levels) and sex (male vs. female). A two‐way MANOVA was used to evaluate differences in the frequency of self‐selected instantaneous speed as related to hormone status and sex. An a priori alpha level of 0.05 was deemed significant for all statistical tests. Significant effects for hormone status [F(1,14) = 17.7, p = 0.001] and sex [F(1,14) = 6.9, p = 0.02] were found for distance. Distance decreased in both sexes following the loss of endogenous sex steroids and females ran more than males regardless of hormone status. Duration was effected by both hormone status [F(1,14) = 19.9, p = 0.001] and sex [F(1,14) = 11.0, p = 0.005]. Overall, duration was less in males and hormone deficiency lead to decreases in running time in both sexes. Speed was potentially affected by hormone status, but was dependent upon sex [F(1,14) = 5.6, p = 0.03], however, follow‐up post‐hoc testing indicated that the loss of hormones had trivial effects on wheel running speed when the parameter was averaged over 24‐hours. A two‐way MANOVA was run to evaluate the effects of sex and hormone status on the selection of instantaneous wheel running speed. No significant effects were found for sex or hormone status, however, the analysis was under powered (power = 0.39 and 0.15) for both variables. In conclusion, 24‐hour averaged distance and duration were affected by hormone status and sex, but 24‐hour averaged speed was not. Trivial differences in self‐selected instantaneous speed may indicate a more nuanced relationship between running speeds and sex or hormone status. A higher‐powered study design is necessary to assess this relationship effectively.