| Sex-associated expression of mouse hepatic and renal CYP2B enzymes by glucocorticoid hormones. | |
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MedLine Citation:
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PMID: 11389874 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The expression of Cyp2b9 and Cyp2b10 genes was investigated in kidney, liver, and cultured hepatocytes of adult C57BL/6NCrj mice. The constitutive expression level of CYP2B mRNA in kidney was higher in female than in male mice, as it was in the liver where more CYP2B9 than CYP2B10 was expressed in the females, and more CYP2B10 was expressed in the males. After treatment with dexamethasone (Dex), induction of CYP2B10 mRNA and protein in the kidneys was far greater in male than in female mice. In contrast to Dex, phenobarbital (PB), pregnenolone-16 alpha-carbonitrile (PCN), and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) did not induce the expression of the Cyp2b gene in the kidneys of either sex. In the liver, PB, PCN, and DDT induced both CYP2B9 and CYP2B10 in both sexes to the same extent, whereas Dex induced only CYP2B10 and simultaneously suppressed CYP2B9. Dex-inducible expression of CYP2B mRNA was decreased by 11 beta-[4-dimethylamino]phenyl-17 beta-hydroxy-17-[1-propynyl]estra-4,9-dien-3-one (RU-486), in both the kidneys and liver from male mice, and in cultured hepatocytes. However, RU-486 itself induced the expression of CYP2B mRNA in female liver and cultured hepatocytes. Interestingly, RU-486 increased PB-inducible expression of these species in cultured hepatocytes. Gonadectomy increased the expression of CYP2B mRNA in untreated male liver, but suppressed Dex-induced expression in the kidneys of both sexes. These observations suggest that (a) there are multiple regulatory pathways in the expression of Cyp2b genes, one of which used by Dex is mediated via the glucocorticoid receptor, which is different from that used by PB, and (b) sex hormones play a role in the regulation of the sex-dependent expression of Cyp2b genes in the mouse. |
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Authors:
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K Jarukamjorn; T Sakuma; M Yamamoto; A Ohara; N Nemoto |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Biochemical pharmacology Volume: 62 ISSN: 0006-2952 ISO Abbreviation: Biochem. Pharmacol. Publication Date: 2001 Jul |
Date Detail:
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Created Date: 2001-06-06 Completed Date: 2001-06-21 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0101032 Medline TA: Biochem Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 161-9 Citation Subset: IM |
Affiliation:
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Department of Toxicology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anticonvulsants / pharmacology Aryl Hydrocarbon Hydroxylases* Cytochrome P-450 Enzyme System / metabolism* Dexamethasone / pharmacology* Dose-Response Relationship, Drug Drug Interactions Electrophoresis Female Gene Expression / drug effects Glucocorticoids / pharmacology Hormone Antagonists / pharmacology Kidney / drug effects*, enzymology Liver / drug effects*, enzymology Male Mice Mice, Inbred C57BL Mifepristone / pharmacology Oxidoreductases, N-Demethylating / metabolism* Phenobarbital / pharmacology RNA, Messenger / metabolism Sex Characteristics |
| Chemical | |
Reg. No./Substance:
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0/Anticonvulsants; 0/Glucocorticoids; 0/Hormone Antagonists; 0/RNA, Messenger; 50-02-2/Dexamethasone; 50-06-6/Phenobarbital; 84371-65-3/Mifepristone; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.14.14.1/Aryl Hydrocarbon Hydroxylases; EC 1.14.14.1/S-mephenytoin N-demethylase; EC 1.5.-/Oxidoreductases, N-Demethylating |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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