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Journal of Molecular Endocrinology (2004) 33 609-622    DOI: 10.1677/jme.1.01508
© 2004 Society for Endocrinology
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Genome-wide expression profiling; a panel of mouse tissues discloses novel biological functions of liver X receptors in adrenals

Knut R Steffensen, Soek Ying Neo1, Thomas M Stulnig2, Vinsensius B Vega1, Safia S Rahman1, Gertrud U Schuster, Jan-Åke Gustafsson and Edison T Liu1

Department of Biosciences, Karolinska Institutet at NOVUM, Huddinge, Sweden
1 Genome Institute of Singapore, 60 Biopolis Street, The Genome, #02-01, Singapore 138672
2 Division of Endocrinology and Metabolism, Department of Internal Medicine III, University of Vienna, and CeMM – Center of Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria

(Requests for offprints should be addressed to K R Steffensen; Email: knut.steffensen{at}biosci.ki.se)

The liver X receptors {alpha} and ß (LXR{alpha} and LXRß ) are members of the nuclear receptor superfamily of proteins which are highly expressed in metabolically active tissues. They regulate gene expression of critical genes involved in cholesterol catabolism and transport, lipid and triglyceride biosynthesis and carbohydrate metabolism in response to distinct oxysterols and intermediates in the cholesterol metabolic pathway. The biological roles of the LXRs in tissues other than liver, intestine and adipose tissue are poorly elucidated. In this study we used global gene-expression profiling analysis to detect differences in expression patterns in several tissues from mice fed an LXR agonist or vehicle. Our results show that LXR plays an important role in the kidney, lung, adrenals, brain, testis and heart where several putative LXR target genes were found. The effects of the LXRs were further analysed in adrenals where treatment with an LXR agonist induced expression of adrenocorticotrophic hormone receptor, suppressed expression of uncoupling protein (UCP)-1 and UCP-3 as well as several glycolytic enzymes and led to increased serum corticosterone levels. These results indicate novel biological roles of the LXR including regulation of energy metabolism, glycolysis and steroidogenesis in the adrenals via alteration of expression profiles of putative target genes.




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