Project
Testosterone and physical activity: mechanisms of action
A body of evidence supports a role for a biological substrate in the disposition to be physically active vs. sedentary. For instance, our observations in the global androgen receptor (AR) knockout mouse as well as the results from castration and replacement studies point that physical activity in male mice is regulated by androgens. Similarly, in humans, low testosterone (T) levels in hypogonadal and androgen-deprived patients have been associated to a diminished self-perceived energy. However, how androgens promote physical exercise remains obscure. Here, our aim is to answer three specific questions about the mechanisms implicated in the androgenic regulation of wheel running and home-cage activity in male mice. First, if T-induced stimulation of activity depends in part of its aromatization into estradiol. Second, to what extent the effects of androgens on exercise are exerted through a central (motivation) independent from a peripheral (stimulation of muscle) action. Finally, if brain dopamine pathways are implicated in the regulation of activity exerted by T. To answer these questions, we will use two animal models: castration plus hormone replacement and mice lacking either the AR or estrogen receptor α specifically in neurons by Cre/LoxP technology. We expect that our findings will help to elucidate the mechanisms involved in the stimulatory effects of androgens on physical activity, hereby contributing to develop novel strategies to promote exercise among patients.