![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 12, No. 20, pp. 3195-3205, October 15, 1998
1 Gene Expression Laboratory, The Salk Institute for
Biological Studies, La Jolla, California 92037;
2 Howard
Hughes Medical Institute (The Salk Institute)
An important requirement for physiologic homeostasis is the
detoxification and removal of endogenous hormones and xenobiotic compounds with biological activity. Much of the detoxification is
performed by cytochrome P-450 enzymes, many of which have broad substrate specificity and are inducible by hundreds of different compounds, including steroids. The ingestion of dietary steroids and
lipids induces the same enzymes; therefore, they would appear to be
integrated into a coordinated metabolic pathway. Instead of possessing
hundreds of receptors, one for each inducing compound, we propose the
existence of a few broad specificity, low-affinity sensing receptors
that would monitor aggregate levels of inducers to trigger production
of metabolizing enzymes. In support of this model, we have isolated a
novel nuclear receptor, termed the steroid and xenobiotic receptor
(SXR), which activates transcription in response to a diversity of
natural and synthetic compounds. SXR forms a heterodimer with RXR that
can bind to and induce transcription from response elements present in
steroid-inducible cytochrome P-450 genes and is expressed in tissues in
which these catabolic enzymes are expressed. These results strongly
support the steroid sensor hypothesis and suggest that broad
specificity sensing receptors may represent a novel branch of the
nuclear receptor superfamily.
[Key Words: Steroid; xenobiotic receptor; nuclear receptor; transcriptional activity]
CiteULike 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  W. Wang, W. W. Prosise, J. Chen, S. S. Taremi, H. V. Le, V. Madison, X. Cui, A. Thomas, K.-C. Cheng, and C. A. Lesburg Construction and characterization of a fully active PXR/SRC-1 tethered protein with increased stability Protein Eng. Des. Sel., July 1, 2008; 21(7): 425 - 433. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Hariparsad, B. A. Carr, R. Evers, and X. Chu Comparison of Immortalized Fa2N-4 Cells and Human Hepatocytes as in Vitro Models for Cytochrome P450 Induction Drug Metab. Dispos., June 1, 2008; 36(6): 1046 - 1055. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. W. Cooper, T. M. Cho, P. M. Thompson, and A. D. Wallace Phthalate Induction of CYP3A4 is Dependent on Glucocorticoid Regulation of PXR Expression Toxicol. Sci., June 1, 2008; 103(2): 268 - 277. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Tompkins, T. L. Sit, and A. D. Wallace Unique Transcription Start Sites and Distinct Promoter Regions Differentiate the Pregnane X Receptor (PXR) Isoforms PXR 1 and PXR 2 Drug Metab. Dispos., May 1, 2008; 36(5): 923 - 929. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Takagi, M. Nakajima, T. Mohri, and T. Yokoi Post-transcriptional Regulation of Human Pregnane X Receptor by Micro-RNA Affects the Expression of Cytochrome P450 3A4 J. Biol. Chem., April 11, 2008; 283(15): 9674 - 9680. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Wang, H. Li, L. B. Moore, M. D. L. Johnson, J. M. Maglich, B. Goodwin, O. R. R. Ittoop, B. Wisely, K. Creech, D. J. Parks, et al. The Phytoestrogen Coumestrol Is a Naturally Occurring Antagonist of the Human Pregnane X Receptor Mol. Endocrinol., April 1, 2008; 22(4): 838 - 857. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Nguyen, J. A. Bonzo, S. Chen, S. Chouinard, M. J. Kelner, G. Hardiman, A. Belanger, and R. H. Tukey Disruption of the Ugt1 Locus in Mice Resembles Human Crigler-Najjar Type I Disease J. Biol. Chem., March 21, 2008; 283(12): 7901 - 7911. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Callaghan, E. Crowley, S. Potter, and I. D. Kerr P-glycoprotein: So Many Ways to Turn It On J. Clin. Pharmacol., March 1, 2008; 48(3): 365 - 378. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Lamba, V. Lamba, S. Strom, R. Venkataramanan, and E. Schuetz Novel Single Nucleotide Polymorphisms in the Promoter and Intron 1 of Human Pregnane X Receptor/NR1I2 and Their Association with CYP3A4 Expression Drug Metab. Dispos., January 1, 2008; 36(1): 169 - 181. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Igarashi, Y. Yogiashi, M. Mihara, I. Takada, H. Kitagawa, and S. Kato Vitamin K Induces Osteoblast Differentiation through Pregnane X Receptor-Mediated Transcriptional Control of the Msx2 Gene Mol. Cell. Biol., November 15, 2007; 27(22): 7947 - 7954. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Chen, Y. Tang, M.-T. Wang, S. Zeng, and D. Nie Human Pregnane X Receptor and Resistance to Chemotherapy in Prostate Cancer Cancer Res., November 1, 2007; 67(21): 10361 - 10367. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-C. Lin, L.-C. Hsieh, M.-W. Kuo, J. Yu, H.-H. Kuo, W.-L. Lo, R.-J. Lin, A. L. Yu, and W.-H. Li Human TRIM71 and Its Nematode Homologue Are Targets of let-7 MicroRNA and Its Zebrafish Orthologue Is Essential for Development Mol. Biol. Evol., November 1, 2007; 24(11): 2525 - 2534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Bhadhprasit, T. Sakuma, N. Hatakeyama, M. Fuwa, K. Kitajima, and N. Nemoto Involvement of Glucocorticoid Receptor and Pregnane X Receptor in the Regulation of Mouse CYP3A44 Female-Predominant Expression by Glucocorticoid Hormone Drug Metab. Dispos., October 1, 2007; 35(10): 1880 - 1885. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kosuge, A. I. Chuang, S. Uematsu, K. P. Tan, K. Ohashi, B. C.B. Ko, and S. Ito Discovery of Osmosensitive Transcriptional Regulation of Human Cytochrome P450 3As by the Tonicity-Responsive Enhancer Binding Protein (Nuclear Factor of Activated T Cells 5) Mol. Pharmacol., October 1, 2007; 72(4): 826 - 837. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Masuyama, H. Nakatsukasa, N. Takamoto, and Y. Hiramatsu Down-Regulation of Pregnane X Receptor Contributes to Cell Growth Inhibition and Apoptosis by Anticancer Agents in Endometrial Cancer Cells Mol. Pharmacol., October 1, 2007; 72(4): 1045 - 1053. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Maeda, M. Oyabu, T. Yotsumoto, R. Higashi, K. Nagata, Y. Yamazoe, and I. Tamai Effect of Pregnane X Receptor Ligand on Pharmacokinetics of Substrates of Organic Cation Transporter Oct1 in Rats Drug Metab. Dispos., September 1, 2007; 35(9): 1580 - 1586. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Lemaire, C. Benod, V. Nahoum, A. Pillon, A.-M. Boussioux, J.-F. Guichou, G. Subra, J.-M. Pascussi, W. Bourguet, A. Chavanieu, et al. Discovery of a Highly Active Ligand of Human Pregnane X Receptor: A Case Study from Pharmacophore Modeling and Virtual Screening to "In Vivo" Biological Activity Mol. Pharmacol., September 1, 2007; 72(3): 572 - 581. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ekins, C. Chang, S. Mani, M. D. Krasowski, E. J. Reschly, M. Iyer, V. Kholodovych, N. Ai, W. J. Welsh, M. Sinz, et al. Human Pregnane X Receptor Antagonists and Agonists Define Molecular Requirements for Different Binding Sites Mol. Pharmacol., September 1, 2007; 72(3): 592 - 603. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Hernandez, W. Huang, L. M. Chapman, S. Chua, D. D. Moore, and W. S. Baldwin The Environmental Estrogen, Nonylphenol, Activates the Constitutive Androstane Receptor Toxicol. Sci., August 1, 2007; 98(2): 416 - 426. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-L. Low, A. M. Dunning, M. Dowsett, E. Folkerd, D. Doody, J. Taylor, A. Bhaniani, R. Luben, K.-T. Khaw, N. J. Wareham, et al. Phytoestrogen Exposure Is Associated with Circulating Sex Hormone Levels in Postmenopausal Women and Interact with ESR1 and NR1I2 Gene Variants Cancer Epidemiol. Biomarkers Prev., May 1, 2007; 16(5): 1009 - 1016. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Matsubara, W. Noracharttiyapot, T. Toriyabe, K. Yoshinari, K. Nagata, and Y. Yamazoe Assessment of Human Pregnane X Receptor Involvement in Pesticide-Mediated Activation of CYP3A4 Gene Drug Metab. Dispos., May 1, 2007; 35(5): 728 - 733. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. K. Pacyniak, X. Cheng, M. L. Cunningham, K. Crofton, C. D. Klaassen, and G. L. Guo The Flame Retardants, Polybrominated Diphenyl Ethers, Are Pregnane X Receptor Activators Toxicol. Sci., May 1, 2007; 97(1): 94 - 102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Xue, L. B. Moore, J. Orans, L. Peng, S. Bencharit, S. A. Kliewer, and M. R. Redinbo Crystal Structure of the Pregnane X Receptor-Estradiol Complex Provides Insights into Endobiotic Recognition Mol. Endocrinol., May 1, 2007; 21(5): 1028 - 1038. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Ozaki, H. Zhang, T. Mizuta, Y. Ide, Y. Eguchi, T. Yasutake, T. Sakamaki, R. G. Pestell, and K. Yamamoto Menatetrenone, a Vitamin K2 Analogue, Inhibits Hepatocellular Carcinoma Cell Growth by Suppressing Cyclin D1 Expression through Inhibition of Nuclear Factor {kappa}B Activation Clin. Cancer Res., April 1, 2007; 13(7): 2236 - 2245. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Ma, Y. Shah, C. Cheung, G. L. Guo, L. Feigenbaum, K. W. Krausz, J. R. Idle, and F. J. Gonzalez The Pregnane X Receptor Gene-Humanized Mouse: A Model for Investigating Drug-Drug Interactions Mediated by Cytochromes P450 3A Drug Metab. Dispos., February 1, 2007; 35(2): 194 - 200. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Hagedorn, C.-L. Cooke, J. R. Falck, B. F. Mitchell, and S. T. Davidge Regulation of Vascular Tone During Pregnancy: A Novel Role for the Pregnane X Receptor Hypertension, February 1, 2007; 49(2): 328 - 333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhai, H. V. Pai, J. Zhou, J. A. Amico, R. R. Vollmer, and W. Xie Activation of Pregnane X Receptor Disrupts Glucocorticoid and Mineralocorticoid Homeostasis Mol. Endocrinol., January 1, 2007; 21(1): 138 - 147. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Zhou, E.-J. Poulton, F. Grun, T. K. Bammler, B. Blumberg, K. E. Thummel, and D. L. Eaton The Dietary Isothiocyanate Sulforaphane Is an Antagonist of the Human Steroid and Xenobiotic Nuclear Receptor Mol. Pharmacol., January 1, 2007; 71(1): 220 - 229. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. MIN Different Modulation of ER-Mediated Transactivation by Xenobiotic Nuclear Receptors Depending on the Estrogen Response Elements and Estrogen Target Cell Types Ann. N.Y. Acad. Sci., December 1, 2006; 1091(1): 244 - 257. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. D. Moore, S. Kato, W. Xie, D. J. Mangelsdorf, D. R. Schmidt, R. Xiao, and S. A. Kliewer International Union of Pharmacology. LXII. The NR1H and NR1I Receptors: Constitutive Androstane Receptor, Pregnene X Receptor, Farnesoid X Receptor {alpha}, Farnesoid X Receptor beta, Liver X Receptor {alpha}, Liver X Receptor beta, and Vitamin D Receptor Pharmacol. Rev., December 1, 2006; 58(4): 742 - 759. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Germain, P. Chambon, G. Eichele, R. M. Evans, M. A. Lazar, M. Leid, A. R. De Lera, R. Lotan, D. J. Mangelsdorf, and H. Gronemeyer International Union of Pharmacology. LXIII. Retinoid X Receptors Pharmacol. Rev., December 1, 2006; 58(4): 760 - 772. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Guintu, M. Kwok, J. J. Hanlon, T. A. Spalding, K. Wolff, H. Yin, K. Kuhen, K. Sasher, P. Calvin, S. Jiang, et al. Just-in-Time Purification: An Effective Solution for Cherry-Picking and Purifying Active Compounds from Large Legacy Libraries J Biomol Screen, December 1, 2006; 11(8): 933 - 939. [Abstract] [PDF]
|
|
|
|
|
|
J. Guzelian, J. L. Barwick, L. Hunter, T. L. Phang, L. C. Quattrochi, and P. S. Guzelian Identification of Genes Controlled by the Pregnane X Receptor by Microarray Analysis of mRNAs from Pregnenolone 16{alpha}-Carbonitrile-Treated Rats Toxicol. Sci., December 1, 2006; 94(2): 379 - 387. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Dinan and R. Lafont Effects and applications of arthropod steroid hormones (ecdysteroids) in mammals. J. Endocrinol., October 1, 2006; 191(1): 1 - 8. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Palanker, A. S. Necakov, H. M. Sampson, R. Ni, C. Hu, C. S. Thummel, and H. M. Krause Dynamic regulation of Drosophila nuclear receptor activity in vivo Development, September 15, 2006; 133(18): 3549 - 3562. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Takeshita, K. Inagaki, J. Igarashi-Migitaka, Y. Ozawa, and N. Koibuchi The endocrine disrupting chemical, diethylhexyl phthalate, activates MDR1 gene expression in human colon cancer LS174T cells. J. Endocrinol., September 1, 2006; 190(3): 897 - 902. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Grun, H. Watanabe, Z. Zamanian, L. Maeda, K. Arima, R. Cubacha, D. M. Gardiner, J. Kanno, T. Iguchi, and B. Blumberg Endocrine-Disrupting Organotin Compounds Are Potent Inducers of Adipogenesis in Vertebrates Mol. Endocrinol., September 1, 2006; 20(9): 2141 - 2155. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Jung, D. J. Mangelsdorf, and U. A. Meyer Pregnane X Receptor Is a Target of Farnesoid X Receptor J. Biol. Chem., July 14, 2006; 281(28): 19081 - 19091. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Wang, A. J. Mendy, G. Dai, H.-R. Luo, L. He, and Y.-J. Y. Wan Retinoids Activate the RXR/SXR-Mediated Pathway and Induce the Endogenous CYP3A4 Activity in Huh7 Human Hepatoma Cells Toxicol. Sci., July 1, 2006; 92(1): 51 - 60. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Meijerman, J. H. Beijnen, and J. H.M. Schellens Herb-Drug Interactions in Oncology: Focus on Mechanisms of Induction Oncologist, July 1, 2006; 11(7): 742 - 752. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Gu, S. Ke, D. Liu, T. Sheng, P. E. Thomas, A. B. Rabson, M. A. Gallo, W. Xie, and Y. Tian Role of NF-{kappa}B in Regulation of PXR-mediated Gene Expression: A MECHANISM FOR THE SUPPRESSION OF CYTOCHROME P-450 3A4 BY PROINFLAMMATORY AGENTS J. Biol. Chem., June 30, 2006; 281(26): 17882 - 17889. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ichikawa, K. Horie-Inoue, K. Ikeda, B. Blumberg, and S. Inoue Steroid and Xenobiotic Receptor SXR Mediates Vitamin K2-activated Transcription of Extracellular Matrix-related Genes and Collagen Accumulation in Osteoblastic Cells J. Biol. Chem., June 23, 2006; 281(25): 16927 - 16934. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Faucette, T. Sueyoshi, C. M. Smith, M. Negishi, E. L. LeCluyse, and H. Wang Differential Regulation of Hepatic CYP2B6 and CYP3A4 Genes by Constitutive Androstane Receptor but Not Pregnane X Receptor J. Pharmacol. Exp. Ther., June 1, 2006; 317(3): 1200 - 1209. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Ding, K. Lichti, and J. L. Staudinger The Mycoestrogen Zearalenone Induces CYP3A through Activation of the Pregnane X Receptor Toxicol. Sci., June 1, 2006; 91(2): 448 - 455. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhou, Y. Zhai, Y. Mu, H. Gong, H. Uppal, D. Toma, S. Ren, R. M. Evans, and W. Xie A Novel Pregnane X Receptor-mediated and Sterol Regulatory Element-binding Protein-independent Lipogenic Pathway J. Biol. Chem., May 26, 2006; 281(21): 15013 - 15020. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Y. Wang, C. W. Li, J. D. Chen, and W. J. Welsh Structural Model Reveals Key Interactions in the Assembly of the Pregnane X Receptor/Corepressor Complex Mol. Pharmacol., May 1, 2006; 69(5): 1513 - 1517. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Tabb and B. Blumberg New Modes of Action for Endocrine-Disrupting Chemicals Mol. Endocrinol., March 1, 2006; 20(3): 475 - 482. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Mu, J. Zhang, S. Zhang, H.-H. Zhou, D. Toma, S. Ren, L. Huang, M. Yaramus, A. Baum, R. Venkataramanan, et al. Traditional Chinese Medicines Wu Wei Zi (Schisandra chinensis Baill) and Gan Cao (Glycyrrhiza uralensis Fisch) Activate Pregnane X Receptor and Increase Warfarin Clearance in Rats J. Pharmacol. Exp. Ther., March 1, 2006; 316(3): 1369 - 1377. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Miki, T. Suzuki, K. Kitada, N. Yabuki, R. Shibuya, T. Moriya, T. Ishida, N. Ohuchi, B. Blumberg, and H. Sasano Expression of the Steroid and Xenobiotic Receptor and Its Possible Target Gene, Organic Anion Transporting Polypeptide-A, in Human Breast Carcinoma Cancer Res., January 1, 2006; 66(1): 535 - 542. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Johnson, C.-W. Li, L.-Y. Chen, J. C. Ghosh, and J. D. Chen Regulation and Binding of Pregnane X Receptor by Nuclear Receptor Corepressor Silencing Mediator of Retinoid and Thyroid Hormone Receptors (SMRT) Mol. Pharmacol., January 1, 2006; 69(1): 99 - 108. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Attar, K.-H. J. Ling, D. D.-S. Tang-Liu, N. Neamati, and V. H. L. Lee Cytochrome P450 3A Expression and Activity in the Rabbit Lacrimal Gland: Glucocorticoid Modulation and the Impact on Androgen Metabolism Invest. Ophthalmol. Vis. Sci., December 1, 2005; 46(12): 4697 - 4706. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Orans, D. G. Teotico, and M. R. Redinbo The Nuclear Xenobiotic Receptor Pregnane X Receptor: Recent Insights and New Challenges Mol. Endocrinol., December 1, 2005; 19(12): 2891 - 2900. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Misawa, J. Inoue, Y. Sugino, H. Hosoi, T. Sugimoto, F. Hosoda, M. Ohki, I. Imoto, and J. Inazawa Methylation-Associated Silencing of the Nuclear Receptor 1I2 Gene in Advanced-Type Neuroblastomas, Identified by Bacterial Artificial Chromosome Array-Based Methylated CpG Island Amplification Cancer Res., November 15, 2005; 65(22): 10233 - 10242. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Minuzzo, M. Ceribelli, M. Pitarque-Marti, S. Borrelli, E. Erba, A. diSilvio, M. D'Incalci, and R. Mantovani Selective Effects of the Anticancer Drug Yondelis (ET-743) on Cell-Cycle Promoters Mol. Pharmacol., November 1, 2005; 68(5): 1496 - 1503. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. J. Komoroski, R. A. Parise, M. J. Egorin, S. C. Strom, and R. Venkataramanan Effect of the St. John's Wort Constituent Hyperforin on Docetaxel Metabolism by Human Hepatocyte Cultures Clin. Cancer Res., October 1, 2005; 11(19): 6972 - 6979. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Mathias, J. Hitti, and J. D. Unadkat P-glycopro |
