This Article Full Text Full Text (PDF) Supplemental Tables All Versions of this Article: 20/5/1138    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart 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 PubMed Alert me to new issues of the journal Download to citation manager NURSA Molecule Pages Link Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jeong, J.-W. Articles by DeMayo, F. J. Search for Related Content PubMed PubMed Citation Articles by Jeong, J.-W. Articles by DeMayo, F. J.

The Genomic Analysis of the Impact of Steroid Receptor Coactivators Ablation on Hepatic Metabolism

Molecular and Cellular Biology (J.-W.J., I.K., K.Y.L., B.W.O’M., F.J.D.), Microarray Core Facility Department of Molecular and Human Genetics (L.D.W.), and Michael E. DeBarkey Department of Surgery (X.-P.W., F.C.B.), Baylor College of Medicine, Houston, Texas 77030

Address all correspondence and requests for reprints to Francesco J. DeMayo, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030. E-mail: fdemayo{at}bcm.tmc.edu.

Members of the steroid receptor coactivator (SRC) family, which include SRC-1 (NcoA-1/p160), SRC-2(TIF2/GRIP1/NcoA-2) and SRC-3(pCIP/RAC3/ACTR/pCIP/ AIB1/TRAM1), are critical mediators of steroid receptor action. Gene ablation studies previously identified SRC-1 and SRC-2 as being involved in the control of energy homeostasis. A more precise identification of the molecular pathways regulated by these coactivators is crucial for understanding the role of steroid receptor coactivators in the control of energy homeostasis and obesity. A genomic approach using microarray analysis was employed to identify the subsets of genes that are altered in the livers of SRC-1^–/–, SRC-2^–/–, and SRC-3^–/– mice. Microarray analysis demonstrates that gene expression changes are specific and nonoverlapping for each SRC member in the liver. The overall pattern of altered gene expressions in the SRC-1^–/– mice was up-regulation, whereas SRC-2^–/– mice showed an overall down-regulation. Several key regulatory enzymes of energy metabolism were significantly altered in the liver of SRC-2^–/– mice, which are consistent with the prior observation that SRC-2^–/– mice have increased energy expenditure. This study demonstrates that the molecular targets of SRC-2 regulation in the murine liver stimulate fatty acid degradation and glycolytic pathway, whereas fatty acid, cholesterol, and steroid biosynthetic pathways are down-regulated.

NURSA Molecule Pages Link:

Coregulators:   SRC-1  |  GRIP1  |  AIB1

This article has been cited by other articles:

				V. Giguere Transcriptional Control of Energy Homeostasis by the Estrogen-Related Receptors Endocr. Rev., October 1, 2008; 29(6): 677 - 696. [Abstract] [Full Text] [PDF]

				D. M. Lonard, R. B. Lanz, and B. W. O'Malley Nuclear Receptor Coregulators and Human Disease Endocr. Rev., August 1, 2007; 28(5): 575 - 587. [Abstract] [Full Text] [PDF]

				A. Mukherjee, S. M. Soyal, R. Fernandez-Valdivia, M. Gehin, P. Chambon, F. J. DeMayo, J. P. Lydon, and B. W. O'Malley Steroid Receptor Coactivator 2 Is Critical for Progesterone-Dependent Uterine Function and Mammary Morphogenesis in the Mouse. Mol. Cell. Biol., September 1, 2006; 26(17): 6571 - 6583. [Abstract] [Full Text] [PDF]