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Crosstalk between the androgen receptor and liver X receptor
Author(s) -
Krycer James Robert,
Brown Andrew John
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.961.2
Subject(s) - liver x receptor , androgen receptor , endocrinology , nuclear receptor , medicine , sterol regulatory element binding protein , androgen , hormone response element , biology , estrogen receptor , liver x receptor alpha , cholesterol , prostate cancer , receptor , cancer research , transcription factor , hormone , sterol , biochemistry , cancer , breast cancer , gene
High cholesterol levels are associated with prostate cancer development. Androgens promote cholesterol accumulation by activating sterol‐regulatory element binding protein (SREBP) transcription factors. However, SREBPs are in balance with the liver X receptor (LXR; NR1H2/NR1H3), a transcription factor that prevents cholesterol accumulation. Here, we show that LXR activity is downregulated by the androgen receptor (NR3C4). In turn, this reduces LXR target gene expression. This antagonism on LXR is exerted by other steroid hormone receptors, including the estrogen, glucocorticoid, and progesterone receptors. We are currently determining the mechanism, and have eliminated effects on LXR mRNA levels, protein degradation or DNA‐binding. However, the androgen receptor does not require protein synthesis to influence LXR, suggesting a direct antagonism. Overall, this androgen‐mediated antagonism of LXR complements SREBP activation, providing a more complete picture as to how androgens increase cellular cholesterol levels in a prostate cancer setting. Given the crosstalk between other steroid hormone receptors and LXR, hormonal regulation of cholesterol via LXR may occur in a variety of cellular contexts. This research is supported by the Prostate Cancer Foundation of Australia, and JRK is the recipient of the Petre Foundation Scholarship.