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Publication : Gene expression profiling reveals a regulatory role for ROR alpha and ROR gamma in phase I and phase II metabolism.

First Author  Kang HS Year  2007
Journal  Physiol Genomics Volume  31
Issue  2 Pages  281-94
PubMed ID  17666523 Mgi Jnum  J:207076
Mgi Id  MGI:5554367 Doi  10.1152/physiolgenomics.00098.2007
Citation  Kang HS, et al. (2007) Gene expression profiling reveals a regulatory role for ROR alpha and ROR gamma in phase I and phase II metabolism. Physiol Genomics 31(2):281-94
abstractText  Retinoid-related orphan receptors alpha (ROR alpha) and gamma (ROR gamma) are both expressed in liver; however, their physiological functions in this tissue have not yet been clearly defined. The ROR alpha1 and ROR gamma 1 isoforms, but not ROR alpha 4, 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 alpha-deficient staggerer (sg) mice (ROR alpha(sg/sg)), ROR gamma(-/-), and ROR alpha(sg/sg)ROR gamma(-/-) double knockout (DKO) mice by microarray analysis. DKO mice were generated to study functional redundancy between ROR alpha and ROR gamma. These analyses demonstrated that ROR alpha and ROR gamma affect the expression of a number of genes. ROR alpha and ROR gamma are particularly important in the regulation of genes encoding several phase I and phase II metabolic enzymes, including several 3beta-hydroxysteroid dehydrogenases, cytochrome P450 enzymes, and sulfotransferases. In addition, our results indicate that ROR alpha and ROR gamma each affect the expression of a specific set of genes but also exhibit functional redundancy. Our study shows that ROR alpha and ROR gamma 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.
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