HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 31/2/281    most recent 00098.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Kang, H. S. Articles by Jetten, A. M. Search for Related Content PubMed PubMed Citation Articles by Kang, H. S. Articles by Jetten, A. M.

Gene expression profiling reveals a regulatory role for ROR and ROR in phase I and phase II metabolism

¹ Cell Biology Section, National Institutes of Health, Research Triangle Park, North Carolina
⁴ Microarray Group, Division of Intramural Research, The National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina
² Stem Cell Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana
³ Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania

Retinoid-related orphan receptors alpha (ROR) and gamma (ROR) are both expressed in liver; however, their physiological functions in this tissue have not yet been clearly defined. The ROR1 and ROR1 isoforms, but not ROR4, show an oscillatory pattern of expression during circadian rhythm. To obtain insight into the physiological functions of ROR receptors in liver, we analyzed the gene expression profiles of livers from WT, ROR-deficient staggerer (sg) mice (ROR^sg/sg), ROR^–/–, and ROR^sg/sgROR^–/– double knockout (DKO) mice by microarray analysis. DKO mice were generated to study functional redundancy between ROR and ROR. These analyses demonstrated that ROR and ROR affect the expression of a number of genes. ROR and ROR are particularly important in the regulation of genes encoding several phase I and phase II metabolic enzymes, including several 3ß-hydroxysteroid dehydrogenases, cytochrome P450 enzymes, and sulfotransferases. In addition, our results indicate that ROR and ROR each affect the expression of a specific set of genes but also exhibit functional redundancy. Our study shows that ROR and ROR receptors influence the regulation of several metabolic pathways, including those involved in the metabolism of steroids, bile acids, and xenobiotics, suggesting that RORs are important in the control of metabolic homeostasis.

liver; nuclear receptor; metabolism; sulfotransferase; staggerer mice; gene expression analysis; circadian rhythm; retinoid-related orphan receptors

This article has been cited by other articles:

				T. Wada, H. S. Kang, M. Angers, H. Gong, S. Bhatia, S. Khadem, S. Ren, E. Ellis, S. C. Strom, A. M. Jetten, et al. Identification of Oxysterol 7{alpha}-Hydroxylase (Cyp7b1) as a Novel Retinoid-Related Orphan Receptor {alpha} (ROR{alpha}) (NR1F1) Target Gene and a Functional Cross-Talk between ROR{alpha} and Liver X Receptor (NR1H3) Mol. Pharmacol., March 1, 2008; 73(3): 891 - 899. [Abstract] [Full Text] [PDF]