![[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. 28, Issue 3, 268-278, March 2000
Department of Pharmaceutical Sciences, St. Jude Children's
Research Hospital, Memphis, Tennessee (E.G.S., C.B., K.Y.); Deutsches
Krebsforschungszentrum, Heidelberg, Federal Republic of Germany (W.S.,
G.S.); Division of Analytical Biochemistry, Faculty of Pharmaceutical
Sciences, Hokkaido University, Kitaku, Sapporo, Hokkaido, Japan (T.K.);
Department of Cellular and Molecular Pharmacology, University of
California, San Francisco, California (L.B.); and Baker Medical
Research Institute, Melbourne, Australia (K.M., T.J.C.)
Cytochrome P-4503A, CYP2B, and P-450 reductase are induced
by glucocorticoids, antiglucocorticoids such as pregnenolone
16
-carbonitrile, and drugs such as rifampin and phenobarbital.
Although the pregnane X receptor is reported to mediate steroid and
drug activation of CYP3A via a conserved cis-element in
CYP3A genes, discrepancies exist between the induction of the
endogenous CYP3A genes and the activation of the pregnane X
receptor. It is a formal possibility that the glucocorticoid
receptor may account for some of these discrepancies. To determine the
requirement in vivo of the glucocorticoid receptor in expression of
CYP3A and CYP2B, we compared the induction of these proteins in the
livers of normal mice and mice with a targeted mutation in the
glucocorticoid receptor. Mice lacking the glucocorticoid receptor show
no difference in constitutive hepatic expression of CYP3A but show a
decrease in the level of CYP2B. Glucocorticoid receptor-deficient mice
challenged with either dexamethasone or pregnenolone 16-carbonitrile
failed to induce CYP2B proteins, whereas CYP2B was readily induced in
(+/+) mice. In contrast, CYP3A and P-450 reductase proteins were
induced by either inducer in wild-type and glucocorticoid receptor-null mice. Similarly, rifampin induced CYP3A in either wild-type or glucocorticoid receptor-null mice. Despite reports that rifampin is a
nonsteroidal ligand for the human glucocorticoid receptor, rifampin
failed to induce tyrosine aminotransferase in mice regardless of
glucocorticoid receptor genotype, and rifampin did not compete for
ligand binding to either mouse or human glucocorticoid receptor. Phenobarbital induced CYP3A, CYP2B, and P-450 reductase in all mice,
but the amplitude of induction was diminished 37% in glucocorticoid receptor-null mice. Thus, there are distinctly different essential requirements of CYP3A, CYP2B, and P-450
reductase genes for the glucocorticoid receptor in their
induction by steroids and drugs.
This article has been cited by other articles:
|
|
 |
|
  E. Audet-Walsh and A. Anderson Dexamethasone Induction of Murine CYP2B Genes Requires the Glucocorticoid Receptor Drug Metab. Dispos., March 1, 2009; 37(3): 580 - 588. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Cheung and F. J. Gonzalez Humanized Mouse Lines and Their Application for Prediction of Human Drug Metabolism and Toxicological Risk Assessment J. Pharmacol. Exp. Ther., November 1, 2008; 327(2): 288 - 299. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Sane, D. J. Buckley, A. R. Buckley, S. C. Nallani, and P. B. Desai Role of Human Pregnane X Receptor in Tamoxifen- and 4-Hydroxytamoxifen-Mediated CYP3A4 Induction in Primary Human Hepatocytes and LS174T Cells Drug Metab. Dispos., May 1, 2008; 36(5): 946 - 954. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Wyde, S. E. Kirwan, F. Zhang, A. Laughter, H. B. Hoffman, E. Bartolucci-Page, K. W. Gaido, B. Yan, and L. You Di-n-Butyl Phthalate Activates Constitutive Androstane Receptor and Pregnane X Receptor and Enhances the Expression of Steroid-Metabolizing Enzymes in the Liver of Rat Fetuses Toxicol. Sci., August 1, 2005; 86(2): 281 - 290. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Sugatani, S. Nishitani, K. Yamakawa, K. Yoshinari, T. Sueyoshi, M. Negishi, and M. Miwa Transcriptional Regulation of Human UGT1A1 Gene Expression: Activated Glucocorticoid Receptor Enhances constitutive Androstane Receptor/Pregnane X Receptor-Mediated UDP-Glucuronosyltransferase 1A1 Regulation with Glucocorticoid Receptor-Interacting Protein 1 Mol. Pharmacol., March 1, 2005; 67(3): 845 - 855. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Swales and M. Negishi CAR, Driving into the Future Mol. Endocrinol., July 1, 2004; 18(7): 1589 - 1598. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Bombail, K. Taylor, G. G. Gibson, and N. Plant ROLE OF Sp1, C/EBP{alpha}, HNF3, AND PXR IN THE BASAL- AND XENOBIOTIC-MEDIATED REGULATION OF THE CYP3A4 GENE Drug Metab. Dispos., May 1, 2004; 32(5): 525 - 535. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Handschin and U. A. Meyer Induction of Drug Metabolism: The Role of Nuclear Receptors Pharmacol. Rev., December 1, 2003; 55(4): 649 - 673. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Zhang, A. F. Purchio, K. Chen, J. Wu, L. Lu, R. Coffee, P. R. Contag, and D. B. West A TRANSGENIC MOUSE MODEL WITH A LUCIFERASE REPORTER FOR STUDYING IN VIVO TRANSCRIPTIONAL REGULATION OF THE HUMAN CYP3A4 GENE Drug Metab. Dispos., August 1, 2003; 31(8): 1054 - 1064. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Wyde, E. Bartolucci, A. Ueda, H. Zhang, B. Yan, M. Negishi, and L. You The Environmental Pollutant 1,1-Dichloro-2,2-bis (p-chlorophenyl)ethylene Induces Rat Hepatic Cytochrome P450 2B and 3A Expression through the Constitutive Androstane Receptor and Pregnane X Receptor Mol. Pharmacol., August 1, 2003; 64(2): 474 - 481. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. R. Mittelstadt and J. D. Ashwell Disruption of Glucocorticoid Receptor Exon 2 Yields a Ligand-Responsive C-Terminal Fragment that Regulates Gene Expression Mol. Endocrinol., August 1, 2003; 17(8): 1534 - 1542. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. M. Arlt, M. Stiborova, A. Hewer, H. H. Schmeiser, and D. H. Phillips Human Enzymes Involved in the Metabolic Activation of the Environmental Contaminant 3-Nitrobenzanthrone: Evidence for Reductive Activation by Human NADPH:Cytochrome P450 Reductase Cancer Res., June 1, 2003; 63(11): 2752 - 2761. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Wang, S. R. Faucette, D. Gilbert, S. L. Jolley, T. Sueyoshi, M. Negishi, and E. L. LeCluyse Glucocorticoid Receptor Enhancement of Pregnane X Receptor-Mediated CYP2B6 Regulation in Primary Human Hepatocytes Drug Metab. Dispos., May 1, 2003; 31(5): 620 - 630. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Pascussi, M. Busson-Le Coniat, P. Maurel, and M.-J. Vilarem Transcriptional Analysis of the Orphan Nuclear Receptor Constitutive Androstane Receptor (NR1I3) Gene Promoter: Identification of a Distal Glucocorticoid Response Element Mol. Endocrinol., January 1, 2003; 17(1): 42 - 55. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. El-Sankary, V. Bombail, G. G. Gibson, and N. Plant Glucocorticoid-Mediated Induction of CYP3A4 is Decreased by Disruption of a Protein: DNA Interaction Distinct from the Pregnane X Receptor Response Element Drug Metab. Dispos., September 1, 2002; 30(9): 1029 - 1034. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Lindley, G. Hamilton, J. S. McCune, S. Faucette, S. S. Shord, R. L. Hawke, H. Wang, D. Gilbert, S. Jolley, B. Yan, et al. The Effect of Cyclophosphamide with and without Dexamethasone on Cytochrome P450 3A4 and 2B6 in Human Hepatocytes Drug Metab. Dispos., July 1, 2002; 30(7): 814 - 822. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Gerbal-Chaloin, M. Daujat, J.-M. Pascussi, L. Pichard-Garcia, M.-J. Vilarem, and P. Maurel Transcriptional Regulation of CYP2C9 Gene. ROLE OF GLUCOCORTICOID RECEPTOR AND CONSTITUTIVE ANDROSTANE RECEPTOR J. Biol. Chem., January 4, 2002; 277(1): 209 - 217. [Abstract] [Full Text]
|
|
|
|
|
|
W. El-Sankary, G. G. Gibson, A. Ayrton, and N. Plant Use of a Reporter Gene Assay to Predict and Rank the Potency and Efficacy of CYP3A4 Inducers Drug Metab. Dispos., November 1, 2001; 29(11): 1499 - 1504. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Handschin, M. Podvinec, R. Looser, R. Amherd, and U. A. Meyer Multiple Enhancer Units Mediate Drug Induction of CYP2H1 by Xenobiotic-Sensing Orphan Nuclear Receptor Chicken Xenobiotic Receptor Mol. Pharmacol., October 1, 2001; 60(4): 681 - 689. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. P. Davidson, S. C. Dogra, and B. K. May The Antiglucocorticoid RU486 Inhibits Phenobarbital Induction of the Chicken CYP2H1 Gene in Primary Hepatocytes Mol. Pharmacol., August 1, 2001; 60(2): 274 - 281. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. C. Quattrochi and P. S. Guzelian CYP3A Regulation: From Pharmacology to Nuclear Receptors Drug Metab. Dispos., April 13, 2001; 29(5): 615 - 622. [Abstract] [Full Text]
|
|
|
|
|
|
J.-M. Pascussi, S. Gerbal-Chaloin, J.-M. Fabre, P. Maurel, and M.-J. Vilarem Dexamethasone Enhances Constitutive Androstane Receptor Expression in Human Hepatocytes: Consequences on Cytochrome P450 Gene Regulation Mol. Pharmacol., April 13, 2001; 58(6): 1441 - 1450. [Abstract] [Full Text]
|
|
 |
 |
 |
|
 |
 |
 |
