The androgen receptor (AR) and the glucocorticoid receptor (GR) have a very similar mechanism of action. Despite these similarities, androgens dampen glucocorticoid-induced muscle atrophy, while they potentiate glucocorticoid responses in adipose tissue. The mechanisms underlying the tissue-specific crosstalk between both hormones remain unknown. Therefore, we investigated in male mice the effect of androgens on the metabolic response to glucocorticoid exposure by 1) lowering androgen levels by castration (ORX) and 2) by analyzing glucocorticoid responses in a global androgen receptor knock out (ARKO) mouse.               
We performed ORX on 14 week-old male mice and supplemented for two weeks with vehicle (VEH), the AR ligand dihydrotestosterone (DHT), the GR ligand corticosterone (CORT) or a combination of both (CORT+DHT). CORT supplementation led to an increase in fat mass (+1.6%) and a decrease in lean mass (-9.4%), while DHT selectively increased lean mass (+0.4%). Interestingly, the addition of DHT to CORT dampened the effect of the latter on lean mass, which decreased to a lesser extent as compared to CORT alone (-3.3%). In contrast, the CORT effect on fat mass was more pronounced in presence of DHT (+4.7%).   
We next supplemented 14 week-old male wild type (WT) and ARKO mice with either VEH or CORT for two weeks. CORT supplementation resulted in an increase in fat mass (+4.2%) and a decrease in lean mass (-7.1%) in the WT animals. In absence of the AR, the increase in fat mass was similar (+5.4%) but the CORT-induced loss of lean mass was less pronounced (-3.2%).              
In conclusion, we confirm a tissue-specific cross-talk between androgens and glucocorticoids, with an additive effect at the level of fat mass and an opposing effect on lean mass. The effect of glucocorticoids on fat mass is very similar in WT versus ARKO, while the effect on lean mass seems stronger when an intact AR is present.