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

Abstract

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.

Keywords: Hormones; locomotion; physical activity; sex steroids.

Figure 1

Experimental timeline to assess the effects of 17β‐estradiol on physical activity and induced urinary bladder distention in male mice.

Figure 2

Wheel running distance (km) prior to orchidectomy (baseline), after removal of endogenous sex steroids (post‐orchidectomy), with 17β‐estradiol treatment (replacement), and during 17β‐estradiol and caudal pressure treatments to alleviate bladder distension between control (n = 5, black bars), low estrogen treated (n = 5, checkered bars), moderate estrogen treated (n = 5, slashed bars), and high estrogen treated (n = 5, open bars) mice. Brackets represent within phase statistical differences (P ≤ 0.05).

Figure 3

Wheel running duration (min) prior to orchidectomy (baseline), after removal of endogenous sex steroids (post‐orchidectomy), with 17β‐estradiol treatment (replacement), and during 17β‐estradiol and caudal pressure treatments to alleviate bladder distension between control (n = 5, black bars), low estrogen treated (n = 5, checkered bars), moderate estrogen treated (n = 5, slashed bars), and high estrogen treated (n = 5, open bars) mice. Brackets represent within phase statistical differences (P ≤ 0.05).

Figure 4

Wheel running speed (m/min) prior to orchidectomy (baseline), after removal of endogenous sex steroids (post‐orchidectomy), with 17β‐estradiol treatment (replacement), and during 17β‐estradiol and caudal pressure treatments to alleviate bladder distension between control (n = 5, black bars), low estrogen treated (n = 5, checkered bars), moderate estrogen treated (n = 5, slashed bars), and high estrogen treated (n = 5, open bars) mice. No significant differences detected (P ≤ 0.05).

Figure 5

Urinary bladder contents (urine fluid mass; g) in mice treated with and without 17β‐estradiol. Control animals (n = 5) were not exposed to exogenous 17β‐estradiol; low estrogen treated (n = 5), moderate estrogen treated (n = 5), and high estrogen treated (n = 5) mice were treated with increasing amounts of 17β‐estradiol. No statistically significant differences were detected between the groups (P ≤ 0.05).