Bisphenol A bis(2,3-dihydroxypropyl) ether (BADGE.2H2O) induces orphan nuclear receptor Nur77 gene expression and increases steroidogenesis in mouse testicular Leydig cells.
Bisphenol A bis (2,3-dihydroxypropyl) ether (BADGE.2H(2)O) is a component of commercial liquid epoxy resins commonly used in the food-packing industry and in dental sealants. There is evidence that it has significant estrogenic activity. Nur77 plays a crucial role in the regulation of certain genes involved in LH-mediated steroidogenesis in testicular Leydig cells. It was previously demonstrated that Bisphenol A (BPA) stimulates Nur77 gene induction and steroidogenesis. In this study, we investigated the effects of BADGE.2H(2)O on Nur77 gene expression and steroidogenesis. Northern blot analysis showed that it increased the expression of Nur77 mRNA and protein, and transient transfection assays demonstrated that it increased the promoter activity and transactivation of Nur77. It also increased the expression of certain steroidogenic genes, such as StAR and 3 beta-HSD. Finally, over-expression of a dominant negative Nur77 cDNA via adenoviral infection reduced BADGE.2H(2)O-mediated progesterone biosynthesis. These results indicate that BADGE.2H(2)O disrupts testicular steroidogenesis by increasing Nur77 gene expression.
Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju, 500-757, Korea.
Seung-Won
SW
Ahn
Balachandar
B
Nedumaran
Yuanbin
Y
Xie
Don-Kyu
DK
Kim
Yong Deuk
YD
Kim
Hueng-Sik
HS
Choi
D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001559:Benzhydryl Compounds; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004852:Epoxy Compounds / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D011987:Receptors, Steroid / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D000098682:Steroidogenic Acute Regulatory Protein; D000098826:Bisphenol A Compounds
D015096:3-Hydroxysteroid Dehydrogenases; D001559:Benzhydryl Compounds; D004268:DNA-Binding Proteins; D004852:Epoxy Compounds; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D010750:Phosphoproteins; D011374:Progesterone; D012333:RNA, Messenger; D011987:Receptors, Steroid; D000098682:Steroidogenic Acute Regulatory Protein; C539818:Nr4a1 protein, mouse; C019273:bisphenol A diglycidyl ether; D000098826:Bisphenol A Compounds