Testosterone stimulates cholesterol clearance from human macrophages by activating LXR?

Low testosterone in men is associated with increased cardiovascular events and mortality. Testosterone has beneficial effects on several risk factors including cholesterol, endothelial dysfunction inflammation as key mediators of atherosclerosis. Although evidence suggests anti-atherogenic, its mechanism action unknown. The present study investigates whether exerts anti-atherogenic by stimulating cholesterol clearance from macrophages via activation liver X receptor (LXR?), a nuclear master regulator cellular homeostasis, lipid regulation, inflammation. Using human monocyte THP-1 cells differentiated into macrophages, the effect (1–10 nM) treatment (24–72 h) expression LXR? LXR- targets apolipoprotein E (APOE), ATP-binding cassette transporter A1 (ABCA1), sterol regulatory element-binding transcription factor 1 (SREBF1) fatty acid synthase (FAS), was investigated qPCR western blotting, or without androgen blockade flutamide LXR antagonism CPPSS-50. Cholesterol measured monitoring fluorescent dehydroergosterol (DHE) ABCA1 translocation observed immunocytochemistry treated macrophages. mRNA protein LXR?, APOE, ABCA1, SREBF1 FAS. These were blocked independently Furthermore stimulated promoted toward cell membrane. acts receptor-dependent pathways to stimulate downstream induce This may, part, explain frequently seen clinically.