Bisphenol A bis(2,3-dihydroxypropyl) ether (BADGE.2H2O) induces orphan nuclear receptor Nur77 gene expression and increases steroidogenesis in mouse testicular Leydig cells

Mol Cells. 2008 Jul 31;26(1):74-80. Epub 2008 Jun 4.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxysteroid Dehydrogenases / genetics
  • 3-Hydroxysteroid Dehydrogenases / metabolism
  • Adenoviridae / genetics
  • Animals
  • Benzhydryl Compounds
  • Blotting, Northern
  • Blotting, Western
  • Cells, Cultured
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Epoxy Compounds / pharmacology*
  • Gene Expression Regulation / drug effects*
  • Leydig Cells / drug effects*
  • Leydig Cells / metabolism
  • Male
  • Mice
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Progesterone / metabolism*
  • Promoter Regions, Genetic
  • RNA, Messenger / metabolism
  • Radioimmunoassay
  • Receptors, Steroid / genetics*
  • Receptors, Steroid / metabolism
  • Transcription, Genetic
  • Transcriptional Activation
  • Transfection

Substances

  • Benzhydryl Compounds
  • DNA-Binding Proteins
  • Epoxy Compounds
  • Nr4a1 protein, mouse
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • Phosphoproteins
  • RNA, Messenger
  • Receptors, Steroid
  • steroidogenic acute regulatory protein
  • Progesterone
  • 3-Hydroxysteroid Dehydrogenases
  • 2,2-bis(4-glycidyloxyphenyl)propane