| Mono-(2-ethylhexyl) phthalate (MEHP) induces nuclear receptor 4A subfamily in NCI-H295R cells: a possible mechanism of aromatase suppression by MEHP. | |
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MedLine Citation:
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PMID: 17574328 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Phthalate esters are widely used as plasticizers for polyvinylchloride and are suspected of functioning as endocrine disrupters. Di-(2-ethylhexyl) phthalate (DEHP), the most important phthalate ester in commercial use, has been reported to act as a rodent reproductive toxicant. In the present study, we investigated the effects of phthalate esters on aromatase (CYP19) activity and on its gene expression in a human adrenocortical carcinoma cell line, NCI-H295R. Mono-(2-ethylhexyl) phthalate (MEHP), a principle metabolite of DEHP, dose-dependently suppressed aromatase activity and its transcription level. Furthermore, MEHP rapidly and transiently induced transcription of the genes which encode nuclear receptor 4A subfamily members (Nur77, Nurr1 and NOR-1), and up-regulated Nur77 promoter activation and Nur77 protein expression in the cells. MEHP-induced Nur77 transcription was inhibited by bisindolylmaleimide I (protein kinase C inhibitor) and wortmannin (phosphoinositide 3-kinase inhibitor). Finally, ectopic expression of Nur77 markedly suppressed forskolin-induced transcriptional activation of promoters I.3 and II of the CYP19 gene. These results suggest that the suppression of aromatase activity and its transcription level by MEHP exposure to NCI-H295R cells was regulated through the rapid and transient expression of Nur77 gene. |
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Authors:
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Mariko Noda; Shuji Ohno; Shizuo Nakajin |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-05-16 |
Journal Detail:
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Title: Molecular and cellular endocrinology Volume: 274 ISSN: 0303-7207 ISO Abbreviation: Mol. Cell. Endocrinol. Publication Date: 2007 Aug |
Date Detail:
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Created Date: 2007-08-06 Completed Date: 2007-10-23 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 7500844 Medline TA: Mol Cell Endocrinol Country: Ireland |
Other Details:
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Languages: eng Pagination: 8-18 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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1-Phosphatidylinositol 3-Kinase
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metabolism Animals Aromatase / genetics, metabolism* Cell Line, Tumor DNA-Binding Proteins / genetics, metabolism* Diethylhexyl Phthalate / pharmacology* Endocrine Disruptors / pharmacology* Gene Expression Regulation / drug effects* Humans Nuclear Receptor Subfamily 4, Group A, Member 1 Plasticizers / pharmacology* Promoter Regions, Genetic Protein Kinase C / metabolism Receptors, Cytoplasmic and Nuclear / genetics, metabolism* Receptors, Steroid / genetics, metabolism* Signal Transduction / physiology Transcription Factors / genetics, metabolism* Transcription, Genetic |
| Chemical | |
Reg. No./Substance:
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0/DNA-Binding Proteins; 0/Endocrine Disruptors; 0/NR4A1 protein, human; 0/Nuclear Receptor Subfamily 4, Group A, Member 1; 0/Plasticizers; 0/Receptors, Cytoplasmic and Nuclear; 0/Receptors, Steroid; 0/Transcription Factors; 117-81-7/Diethylhexyl Phthalate; EC 1.14.14.1/Aromatase; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.11.13/Protein Kinase C |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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