ArticleThe Journal of biological chemistry2011
Cross-talk between the androgen receptor and the liver X receptor: implications for cholesterol homeostasis.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed.
- Small Molecule Liver X Receptor Modulator GAC0001E5 Targets Mechanisms of Endocrine Resistance in Estrogen Receptor-Positive Breast Cancer Cells.Biomolecules · 2026Article
- Comprehensive analysis of cholesterol metabolism-related genes in prostate cancer: integrated analysis of single-cell and bulk RNA sequencing.Discover oncology · 2025Article
- Article
- Oxysterols as Biomarkers of Aging and Disease.Advances in experimental medicine and biology · 2024Article
- Article
- Lipid Metabolic Disorders in Neurodegenerative Diseases - Role of Androgen Receptor.The Eurasian journal of medicine · 2023Review
- Efficient and reproducible generation of human induced pluripotent stem cell-derived expandable liver organoids for disease modeling.Scientific reports · 2023Article
- Estrogen receptors and the aging brain.Essays in biochemistry · 2021Review
- Review
- Prostate Cancer-Focus on Cholesterol.Cancers · 2021Review
- Sendai Virus-Vectored Vaccines That Express Envelope Glycoproteins of Respiratory Viruses.Viruses · 2021Review
- Lipidomic-Based Advances in Diagnosis and Modulation of Immune Response to Cancer.Metabolites · 2020Review
- Anabolic androgenic steroids exert a selective remodeling of the plasma lipidome that mirrors the decrease of the de novo lipogenesis in the liver.Metabolomics : Official journal of the Metabolomic Society · 2020Article
- Lactate production is a prioritized feature of adipocyte metabolism.The Journal of biological chemistry · 2020Article
- Serine 474 phosphorylation is essential for maximal Akt2 kinase activity in adipocytes.The Journal of biological chemistry · 2019Article
- Prostate Cancer Energetics and Biosynthesis.Advances in experimental medicine and biology · 2019Review
- New Insights in Prostate Cancer Development and Tumor Therapy: Modulation of Nuclear Receptors and the Specific Role of Liver X Receptors.International journal of molecular sciences · 2018Review
- LXR/RXR signaling and neutrophil phenotype following myocardial infarction classify sex differences in remodeling.Basic research in cardiology · 2018Article
- Androgen receptor overexpression in prostate cancer in type 2 diabetes.Molecular metabolism · 2018Article
- The transcriptional response to oxidative stress is part of, but not sufficient for, insulin resistance in adipocytes.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High cholesterol levels are associated with prostate cancer development. Androgens promote cholesterol accumulation by activating the sterol-regulatory element-binding protein isoform 2 (SREBP-2) transcription factor. However, SREBP-2 is in balance with the liver X receptor (LXR; NR1H2/NR1H3), a transcription factor that prevents cholesterol accumulation. Here, we show that LXR activity is down-regulated by the androgen receptor (AR; NR3C4). In turn, this reduces LXR target gene expression. This antagonism on LXR is also exerted by other steroid hormone receptors, including the estrogen, glucocorticoid, and progesterone receptors. This suggests a generalizable mechanism, but the AR does not affect LXR mRNA levels, protein degradation, or DNA binding. We also found that the AR does not require protein synthesis to influence LXR, suggesting a direct antagonism. However, the AR does not directly bind LXR. The AR N-terminal domain (involved in transactivation), but not its DNA-binding domain, is required to suppress LXR activity, suggesting coactivator competition. Overall, this androgen-mediated antagonism of LXR complements SREBP-2 activation, providing a more complete picture as to how androgens increase cellular cholesterol levels in a prostate cancer setting. Given the cross-talk between other steroid hormone receptors and LXR, hormonal regulation of cholesterol via LXR may occur in a variety of cellular contexts.
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