[What!] [Mice] Androgen Action Via The Androgen Receptor In Neurons Within The Brain Davey RA, Clarke MV, Russell PK, et al. Androgen action via the Androgen Receptor in neurons within the brain positively regulates muscle mass in male mice. Endocrinology. https://academic.oup.com/endo/article-abstract/doi/10.1210/en.2017-00470/4056265/Androgen-action-via-the-Androgen-Receptor-in
Whilst it is well established that exogenous androgens have anabolic effects on skeletal muscle mass in humans and mice, data from muscle-specific androgen receptor knock out (ARKO) mice indicate that myocytic expression of the AR is dispensable for hind-limb muscle mass accrual in males.
To identify possible indirect actions of androgens via the AR in neurons to regulate muscle, we generated neuron-ARKO mice where the dominant DNA binding-dependent actions of the AR are deleted in neurons of the cortex, forebrain, hypothalamus and olfactory bulb.
Serum testosterone and luteinizing hormone levels were elevated 2-fold in neuron-ARKO males compared to wild-type littermates due to disruption of negative feedback to the hypothalamic-pituitary-gonadal axis.
Despite this increase in serum testosterone levels which was expected to increase muscle mass, the mass of the mixed-fibre gastrocnemius and the fast-twitch fibre extensor digitorum longus hind-limb muscles were decreased by 10% in neuron-ARKOs at 12 weeks of age while muscle strength and fatigue of the Gast was unaffected.
The mass of the soleus muscle however, which consists of a high proportion of slow-twitch fibres, was unaffected in neuron-ARKOs demonstrating a stimulatory action of androgens via the AR in neurons to increase the mass of fast-twitch hind-limb muscles. Furthermore neuron-ARKOs displayed reductions in voluntary and involuntary physical activity by up to 60%.
These data provide the first evidence for a role of androgens via the AR in neurons to positively regulate fast-twitch hind-limb muscle mass and physical activity in male mice.
Whilst it is well established that exogenous androgens have anabolic effects on skeletal muscle mass in humans and mice, data from muscle-specific androgen receptor knock out (ARKO) mice indicate that myocytic expression of the AR is dispensable for hind-limb muscle mass accrual in males.
To identify possible indirect actions of androgens via the AR in neurons to regulate muscle, we generated neuron-ARKO mice where the dominant DNA binding-dependent actions of the AR are deleted in neurons of the cortex, forebrain, hypothalamus and olfactory bulb.
Serum testosterone and luteinizing hormone levels were elevated 2-fold in neuron-ARKO males compared to wild-type littermates due to disruption of negative feedback to the hypothalamic-pituitary-gonadal axis.
Despite this increase in serum testosterone levels which was expected to increase muscle mass, the mass of the mixed-fibre gastrocnemius and the fast-twitch fibre extensor digitorum longus hind-limb muscles were decreased by 10% in neuron-ARKOs at 12 weeks of age while muscle strength and fatigue of the Gast was unaffected.
The mass of the soleus muscle however, which consists of a high proportion of slow-twitch fibres, was unaffected in neuron-ARKOs demonstrating a stimulatory action of androgens via the AR in neurons to increase the mass of fast-twitch hind-limb muscles. Furthermore neuron-ARKOs displayed reductions in voluntary and involuntary physical activity by up to 60%.
These data provide the first evidence for a role of androgens via the AR in neurons to positively regulate fast-twitch hind-limb muscle mass and physical activity in male mice.
