Testosterone stimulates cholesterol clearance from human macrophages by activating LXRα

Area of Science:

• Endocrinology
• Cardiovascular Biology
• Molecular Biology

Background:

• Low testosterone is linked to increased cardiovascular events and mortality.
• Testosterone influences cardiovascular risk factors like cholesterol, endothelial dysfunction, and inflammation.
• The anti-atherogenic mechanism of testosterone is not fully understood.

Purpose of the Study:

• To investigate if testosterone reduces atherosclerosis by promoting macrophage cholesterol clearance.
• To determine if testosterone activates liver X receptor alpha (LXRα) in this process.

Main Methods:

• Human THP-1 cells differentiated into macrophages were treated with testosterone.
• Gene and protein expression of LXRα and its targets (APOE, ABCA1, SREBF1, FAS) were analyzed.
• Cholesterol clearance and ABCA1 translocation were measured, with and without receptor blockade.

Main Results:

• Testosterone increased LXRα, APOE, ABCA1, SREBF1, and FAS expression.
• These effects were blocked by androgen receptor and LXR antagonism.
• Testosterone stimulated macrophage cholesterol clearance and ABCA1 membrane translocation.

Conclusions:

• Testosterone promotes cholesterol clearance in macrophages via androgen receptor-dependent LXRα activation.
• This pathway may contribute to the observed anti-atherogenic effects of testosterone in clinical settings.