Effects of Aromatase Inhibition on the Physical Activity Levels of Male Mice

Abstract

Increasing activity levels in an inactive population can lead to associative increases in health and well-being. Both biologic and genetic factors have been identified that alter physical activity levels in humans and rodents with an extensive early literature regarding sex steroid effects on physical activity. Currently, it is suggested that the androgens require conversion to estrogens prior to eliciting any effects on activity patterns. Recent data contradicts this assertion; thus, the purpose of this study was to evaluate the necessity of the aromatase complex in activity regulation. Wheel running was assessed in male C57BL/6J mice under various sex steroid-disrupted and aromatase-inhibited conditions. Inhibition of the aromatase complex was achieved through administration of two different aromatase inhibiting substances-letrozole and exemestane. Wheel running was unaffected by aromatase inhibition in reproductively intact and sex steroid supplemented mice. Orchidectomy significantly reduced wheel running activity. Steroid replacement recovered wheel running to pre-surgical levels; however, aromatase inhibition did not further affect wheel running levels. The recovery of wheel running in mice with androgen supplementation and the further persistence of wheel running in mice with compromised aromatase function suggests that the androgens-testosterone in particular-may directly affect wheel running patterns in male mice.

Keywords: Exemestane; Letrozole; Locomotion; Sex Hormone; Sex Steroid.

Figure 1

The experimental timelines (days) for assessing physical activity levels in aromatase inhibited and sex steroid modified mice. Black bars represent recovery periods—after surgeries and after cessation of injections—in which running wheels were not in the cages.

Figure 2

Wheel running indices for male C57BL/6J mice at baseline, during injections, and during post-injection clearance. White bars denote control mice (n=10) that received vehicle injections and black bars denote experimentally treated mice (n=10) that received exemestane (panels a–c; distance, duration, speed) or letrozole (panel d; distance) injections.

Figure 3

Wheel running indices (distance, duration, and speed) for male C57BL/6J mice at baseline, during injections, and during injections supplemented with either testosterone or 17β-estradiol. White bars denote control mice (n=9) that received vehicle injections and empty silastic implants. Checkered bars denote experimentally treated mice (n=10) that received exemestane injections and silastic implants containing testosterone. Black bars denote experimentally treated mice (n=10) that received exemestane injections and silastic implants containing 17β-estradiol.

Figure 4

Wheel running indices (distance, duration, and speed) for male C57BL/6J mice at baseline, during injections, during steroid replacement, and during steroid replacement with injections. White bars denote control mice (n=10) that received vehicle injections and empty silastic implants. Checkered bars denote experimentally treated mice (n=10) that received silastic implants containing testosterone and exemestane injections. Black bars denote experimentally treated mice (n=10) that received silastic implants containing 17β-estradiol and exemestane injections. *=significantly different from controls and baseline values.