Estrogen receptor-related orphan receptor alpha 1 is a member of the steroid/thyroid nuclear receptor superfamily. We have previously cloned the human estrogen receptor-related orphan receptor alpha 1 (hERR alpha 1) cDNA and demonstrated that it enhances estrogen responsiveness of the lactoferrin gene promoter in transfected human endometrial carcinoma cells. In the present study, we used the hERR alpha 1 cDNA as a probe and isolated the mouse homologue of ERR alpha 1 from the cDNA libraries of the brain and kidney. Sequence comparison between human and mouse ERR alpha 1 (mERR alpha 1) revealed that the homologies are 89% in nucleotides and 97% in amino acids. By electrophoresis mobility shift assay, we showed that the glutathione S-transferase-mERR alpha 1 fusion protein produced in a bacterial system bound to the human ERR alpha 1 DNA-binding element. Mouse uterine nuclear extract also interacted with this DNA element and produced three complexes in the mobility shift assay, one of which was supershifted by the hERR alpha 1 antiserum. A 2.2 kbp transcript was detected by Northern analysis in all adult mouse tissues tested; however, large variations in the amount of ERR alpha 1 mRNA were found among them. Multiple immunoreactive forms of mouse ERR alpha 1 were detected by Western analysis in non-reproductive tissues, whereas a major 53 kDa protein was found in reproductive tissues such as uterus, cervix and vagina. Diethylstilbestrol (DES) stimulated the expression of ERR alpha 1 mRNA in the uterus of 19-day-old mouse. We showed that DES and estradiol, but not progesterone or dexamethasone, enhanced the level of immunoreactive ERR alpha 1 in the mouse uterus. These results demonstrated that the ERR alpha 1 is an estrogen-responsive gene in the mouse uterus and provides a model system with which to study the biological roles of this nuclear orphan receptor.

This article has been cited by other articles:

				C. Teyssier, S. Bianco, O. Lanvin, and J.-M. Vanacker The orphan receptor ERR{alpha} interferes with steroid signaling Nucleic Acids Res., August 12, 2008; (2008) gkn520v1. [Abstract] [Full Text] [PDF]

				P. Hu, H. K. Kinyamu, L. Wang, J. Martin, T. K. Archer, and C. Teng Estrogen Induces Estrogen-related Receptor {alpha} Gene Expression and Chromatin Structural Changes in Estrogen Receptor (ER)-positive and ER-negative Breast Cancer Cells J. Biol. Chem., March 14, 2008; 283(11): 6752 - 6763. [Abstract] [Full Text] [PDF]

				R. A Zirngibl, J. S M Chan, and J. E Aubin Estrogen receptor-related receptor {alpha} (ERR{alpha}) regulates osteopontin expression through a non-canonical ERR{alpha} response element in a cell context-dependent manner J. Mol. Endocrinol., February 1, 2008; 40(2): 61 - 73. [Abstract] [Full Text] [PDF]

				O. Lanvin, S. Bianco, N. Kersual, D. Chalbos, and J.-M. Vanacker Potentiation of ICI182,780 (Fulvestrant)-induced Estrogen Receptor-{alpha} Degradation by the Estrogen Receptor-related Receptor-{alpha} Inverse Agonist XCT790 J. Biol. Chem., September 28, 2007; 282(39): 28328 - 28334. [Abstract] [Full Text] [PDF]

				E. Bonnelye, R. A. Zirngibl, P. Jurdic, and J. E. Aubin The Orphan Nuclear Estrogen Receptor-Related Receptor-{alpha} Regulates Cartilage Formation in Vitro: Implication of Sox9 Endocrinology, March 1, 2007; 148(3): 1195 - 1205. [Abstract] [Full Text] [PDF]

				G. Benoit, A. Cooney, V. Giguere, H. Ingraham, M. Lazar, G. Muscat, T. Perlmann, J.-P. Renaud, J. Schwabe, F. Sladek, et al. International Union of Pharmacology. LXVI. Orphan Nuclear Receptors Pharmacol. Rev., December 1, 2006; 58(4): 798 - 836. [Abstract] [Full Text] [PDF]

				A M Tarrant, S R Greytak, G V Callard, and M E Hahn Estrogen receptor-related receptors in the killifish Fundulus heteroclitus: diversity, expression, and estrogen responsiveness. J. Mol. Endocrinol., August 1, 2006; 37(1): 105 - 120. [Abstract] [Full Text] [PDF]

				Z. Zhang, K. Chen, J. C. Shih, and C. T. Teng Estrogen-Related Receptors-Stimulated Monoamine Oxidase B Promoter Activity Is Down-Regulated by Estrogen Receptors Mol. Endocrinol., July 1, 2006; 20(7): 1547 - 1561. [Abstract] [Full Text] [PDF]

				J. B. Barry, J. Laganiere, and V. Giguere A Single Nucleotide in an Estrogen-Related Receptor {alpha} Site Can Dictate Mode of Binding and Peroxisome Proliferator-Activated Receptor {gamma} Coactivator 1{alpha} Activation of Target Promoters Mol. Endocrinol., February 1, 2006; 20(2): 302 - 310. [Abstract] [Full Text] [PDF]

				J. Seely, K. S. Amigh, T. Suzuki, B. Mayhew, H. Sasano, V. Giguere, J. Laganiere, B. R. Carr, and W. E. Rainey Transcriptional Regulation of Dehydroepiandrosterone Sulfotransferase (SULT2A1) by Estrogen-Related Receptor {alpha} Endocrinology, August 1, 2005; 146(8): 3605 - 3613. [Abstract] [Full Text] [PDF]

				E E Connor, D L Wood, T S Sonstegard, A F da Mota, G L Bennett, J L Williams, and A V Capuco Chromosomal mapping and quantitative analysis of estrogen-related receptor alpha-1, estrogen receptors alpha and beta and progesterone receptor in the bovine mammary gland J. Endocrinol., June 1, 2005; 185(3): 593 - 603. [Abstract] [Full Text] [PDF]

				E. Bonnelye and J. E. Aubin Estrogen Receptor-Related Receptor {alpha}: A Mediator of Estrogen Response in Bone J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 3115 - 3121. [Abstract] [Full Text] [PDF]

				D Liu, Z Zhang, and C T Teng Estrogen-related receptor-{gamma} and peroxisome proliferator-activated receptor-{gamma} coactivator-1{alpha} regulate estrogen-related receptor-{alpha} gene expression via a conserved multi-hormone response element J. Mol. Endocrinol., April 1, 2005; 34(2): 473 - 487. [Abstract] [Full Text] [PDF]

				C. P. Cheung, S. Yu, K. B. Wong, L. W. Chan, F. M. M. Lai, X. Wang, M. Suetsugi, S. Chen, and F. L. Chan Expression and Functional Study of Estrogen Receptor-Related Receptors in Human Prostatic Cells and Tissues J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1830 - 1844. [Abstract] [Full Text] [PDF]

				D. Sumi and L. J. Ignarro Estrogen-related receptor {alpha}1 up-regulates endothelial nitric oxide synthase expression PNAS, November 25, 2003; 100(24): 14451 - 14456. [Abstract] [Full Text] [PDF]

				D. Liu, Z. Zhang, W. Gladwell, and C. T. Teng Estrogen Stimulates Estrogen-Related Receptor {alpha} Gene Expression through Conserved Hormone Response Elements Endocrinology, November 1, 2003; 144(11): 4894 - 4904. [Abstract] [Full Text] [PDF]

				Y. Kamei, H. Ohizumi, Y. Fujitani, T. Nemoto, T. Tanaka, N. Takahashi, T. Kawada, M. Miyoshi, O. Ezaki, and A. Kakizuka PPAR{gamma} coactivator 1{beta}/ERR ligand 1 is an ERR protein ligand, whose expression induces a high-energy expenditure and antagonizes obesity PNAS, October 14, 2003; 100(21): 12378 - 12383. [Abstract] [Full Text] [PDF]

				S. N. Schreiber, D. Knutti, K. Brogli, T. Uhlmann, and A. Kralli The Transcriptional Coactivator PGC-1 Regulates the Expression and Activity of the Orphan Nuclear Receptor Estrogen-Related Receptor alpha (ERRalpha ) J. Biol. Chem., March 7, 2003; 278(11): 9013 - 9018. [Abstract] [Full Text] [PDF]

				C. T. Teng, C. Beard, and W. Gladwell Differential Expression and Estrogen Response of Lactoferrin Gene in the Female Reproductive Tract of Mouse, Rat, and Hamster Biol Reprod, November 1, 2002; 67(5): 1439 - 1449. [Abstract] [Full Text] [PDF]

				E. Bonnelye, V. Kung, C. Laplace, D. L. Galson, and J. E. Aubin Estrogen Receptor-Related Receptor {alpha} Impinges on the Estrogen Axis in Bone: Potential Function in Osteoporosis Endocrinology, September 1, 2002; 143(9): 3658 - 3670. [Abstract] [Full Text] [PDF]

				R. J. Kraus, E. A. Ariazi, M. L. Farrell, and J. E. Mertz Estrogen-related Receptor alpha 1 Actively Antagonizes Estrogen Receptor-regulated Transcription in MCF-7 Mammary Cells J. Biol. Chem., June 28, 2002; 277(27): 24826 - 24834. [Abstract] [Full Text] [PDF]

				S. Nilsson, S. Makela, E. Treuter, M. Tujague, J. Thomsen, G. Andersson, E. Enmark, K. Pettersson, M. Warner, and J.-A. Gustafsson Mechanisms of Estrogen Action Physiol Rev, October 1, 2001; 81(4): 1535 - 1565. [Abstract] [Full Text] [PDF]

				E. Bonnelye, L. Merdad, V. Kung, and J.E. Aubin The Orphan Nuclear Estrogen Receptor-related Receptor {alpha} (ERR{alpha}) Is Expressed throughout Osteoblast Differentiation and Regulates Bone Formation In Vitro J. Cell Biol., May 21, 2001; 153(5): 971 - 984. [Abstract] [Full Text] [PDF]

				D. J. Heard, P. L. Norby, J. Holloway, and H. Vissing Human ERR{gamma}, a Third Member of the Estrogen Receptor-Related Receptor (ERR) Subfamily of Orphan Nuclear Receptors: Tissue-Specific Isoforms Are Expressed during Development and in the Adult Mol. Endocrinol., March 1, 2000; 14(3): 382 - 392. [Abstract] [Full Text]

				Z. Zhang and C. T. Teng Estrogen Receptor-related Receptor alpha 1 Interacts with Coactivator and Constitutively Activates the Estrogen Response Elements of the Human Lactoferrin Gene J. Biol. Chem., June 30, 2000; 275(27): 20837 - 20846. [Abstract] [Full Text] [PDF]

				Z. Yan and A. M. Jetten Characterization of the Repressor Function of the Nuclear Orphan Receptor Retinoid Receptor-related Testis-associated Receptor/Germ Cell Nuclear Factor J. Biol. Chem., November 3, 2000; 275(45): 35077 - 35085. [Abstract] [Full Text] [PDF]