Effects of varying doses of estrogen and caudal pressure on wheel running in orchidectomized male mice.

Physical inactivity is a leading cause of hypokinetic diseases - obesity, heart disease, diabetes, and certain types of cancers. Increased city walkability, better access to fitness facilities, and remediation of socioeconomic barriers prove successful for limited populations within the confines of stringently controlled environments; however, these strategies fail to reverse the ever-increasing physical inactivity epidemic on a global scale indicating the existence of other unidentified factors. These purported biological factors remain critical targets to understand the regulation of this complex phenotype. An estrogenic mechanism that incompletely or slowly adjusts physical activity levels following reintroduction of estrogenic compounds to surgically gonadectomized mice has been postulated to exist. Currently, this mechanism remains scrutinized due to concerns that elevated estrogen levels induce urinary bladder distension. The distension of the urinary bladder may mechanically disrupt physical activity, masking any physiological effects estrogen has on physical activity. The purpose of this study was to evaluate the effects of estrogen on physical activity levels while employing dose-related strategies to alleviate distension in mice. Wheel running data were collected under normal physiological conditions, following removal of endogenous sex steroids via orchidectomy, and during estrogen replacement at various doses (0%, 10%, 50% or 100% estrogen-containing implants) to induce varying degrees of urinary bladder distension. Wheel running distance (P = 0.005) and duration (P = 0.006) decreased after orchidectomy, but slowly increased following estrogen replacement. During the study, wheel running did not return to the levels observed in physiologically intact mice. Significant distension was not observed between estrogen treatment groups indicating that a slow-responding estrogen effect exists in male mice that prevents wheel running from returning to normal levels immediately following steroid reintroduction. The limited increase in wheel running during estrogen treatment following orchidectomy is not an artifact of induced urinary bladder distension.

Prolonged Effects of Elevated 17ß-Estradiol on Physical Activity after Orchidectomy.

The biological mechanisms regulating physical activity patterns appear to be linked to the sex hormones. Elucidation of these regulatory mechanisms may enhance individual physical activity patterns producing positive gains in health. PURPOSE: The purpose of this study was to evaluate the prolonged effects of estrogen on wheel running distance, duration, and speed in orchidectomized mice. METHODS: The physical activity patterns of 9-wk-old C57BL/6j male mice (n = 28) were observed. Wheel running distance, duration, and speed were assessed under physiological conditions for 7 d. Next, physical activity patterns were evaluated after bilateral orchidectomy (n = 14) or sham orchidectomy (n = 14) for an additional 7 d. Orchidectomized mice were provided estrogen containing capsules for three additional weeks; control mice were provided estrogen-free capsules. Wheel running distance, duration, and speed were analyzed by three two-way (treatment group-phase of study) analysis of variance tests. RESULTS: Wheel running speed was unaffected by sex hormone status. Distance (mean ± SD = 6.74 ± 2.13 km at baseline) decreased significantly after orchidectomy (2.27 ± 1.55 km) and remained low after initial estrogen treatment (3.04 ± 1.05 km). Prolonged estrogen exposure sustained a significant elevation of daily distance (4.47 ± 1.87 km). Prolonged estrogen exposure recovered and significantly sustained wheel running duration (baseline, 248 ± 60 min; postorchidectomy, 102 ± 53 min; prolonged exposure, 170 ± 63 min). CONCLUSIONS: Wheel running behavior was reduced significantly after orchidectomy and remained low after initial treatment with estrogens, but recovered to near control levels after 2 wk of exposure to estrogens. The estrogenic mechanism regulating wheel running behavior in male mice appears to induce an extensive but slow acting biological mechanism. Understanding the biological drive behind this mechanism may aid in developing useful therapeutic strategies to combat health issues related to physical inactivity.

Stabilization of the wheel running phenotype in mice.

PURPOSE: Increased physical activity is well known to improve health and wellness by modifying the risks for many chronic diseases. Rodent wheel running behavior is a beneficial surrogate model to evaluate the biology of daily physical activity in humans. Upon initial exposure to a running wheel, individual mice differentially respond to the experience, which confounds the normal activity patterns exhibited in this otherwise repeatable phenotype. To promote phenotypic stability, a minimum seven-day (or greater) acclimation period is utilized. Although phenotypic stabilization is achieved during this 7-day period, data to support acclimation periods of this length are not currently available in the literature. The purpose of this project is to evaluate the wheel running response in C57BL/6j mice immediately following exposure to a running wheel. METHODS: Twenty-eight male and thirty female C57BL/6j mice (Jackson Laboratory, Bar Harbor, ME) were acquired at eight weeks of age and were housed individually with free access to running wheels. Wheel running distance (km), duration (min), and speed (m∙min(-1)) were measured daily for fourteen days following initial housing. One-way ANOVAs were used to evaluate day-to-day differences in each wheel running character. Limits of agreement and mean difference statistics were calculated between days 1-13 (acclimating) and day 14 (acclimated) to assess day-to-day agreement between each parameter. RESULTS: Wheel running distance (males: F=5.653, p=2.14 × 10(-9); females: F=8.217, p=1.20 × 10(-14)), duration (males: F=2.613, p=0.001; females: F=4.529, p=3.28 × 10(-7)), and speed (males: F=7.803, p=1.22 × 10(-13); females: F=13.140, p=2.00 × 10(-16)) exhibited day-to-day differences. Tukey's HSD post-hoc testing indicated differences between early (males: days 1-3; females: days 1-6) and later (males: days >3; females: days >6) wheel running periods in distance and speed. Duration only exhibited an anomalous difference between wheel running on day 13 and wheel running on days 1 through 4 in males. In females, duration exhibited anomalous differences due to abnormally depressed wheel running on day 6 and abnormally elevated wheel running on day 14. Limits of agreement and mean difference statistics indicated stable phenotypic variability with an up-trending daily mean for distance and speed that stabilized within the first three days in males and within eight days in females. Duration exhibited stable variability after nine days in males and after seven days in females. CONCLUSION: Although it is common practice to allow a prolonged (≥ seven day) acclimation period prior to recording wheel running data, the current study suggests that phenotypic stabilization of all three indices is achieved at different times with distance and speed exhibiting stability by day three in males and day eight in females. Duration exhibits stability by day nine in males and day seven in females.