title: Bisphenol A induces differentiation of human preadipocytes in the absence of glucocorticoid and is inhibited by an estrogen-receptor antagonist.
abstract: BACKGROUND
  Obesity is a major health concern in the developed world, and increasing evidence suggests that exposures to common environmental substances may enhance the risk for the development of this disease.
  
  
  OBJECTIVE
  The current study examines the effect of the ubiquitous plastic monomer bisphenol A (BPA) on the differentiation of primary human preadipocytes in vitro and the role of the estrogen and glucocorticoid receptors.
  
  
  METHODS
  In this study, the mechanism of BPA-induced adipogenesis in preadipocytes from donors with healthy body mass index in the absence of exogenous glucocorticoid was evaluated. The effects of estradiol, the estrogen-receptor (ER) antagonist ICI and the glucocorticoid receptor (GR) antagonist RU486 on BPA-induced adipogenesis were examined. The expression levels of key adipogenic factors were assessed.
  
  
  RESULTS
  Treatment of preadipocytes with 1-50 μM BPA induced a dose-dependent increase in differentiation and lipid accumulation as determined by lipid staining and triacylglyceride quantification. BPA also induced expression of the adipogenic markers aP2, adipsin, peroxisome proliferator-activated receptor γ and the CCAAT-enhancer-binding proteins α and β. Co-treatment of cells with ICI inhibited the BPA-induced increase in aP2 levels, while treatment with ICI or estradiol alone had no effect. Treatment of cells with the GR antagonist RU486 had no effect on BPA-induced differentiation as evaluated by aP2 levels.
  
  
  CONCLUSIONS
  This study is one of the first to show that BPA induces human adipocyte differentiation in the absence of exogenous glucocorticoid through a non-classical ER pathway rather than through GR activation. These studies add to the growing evidence that endocrine-disrupting chemicals such as BPA have the potential to modulate adipogenesis and impact human biology.
authors.affiliation: In Vitro Molecular Toxicology Laboratory, Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, Canada.
authors.forename: J G
authors.initials: JG
authors.lastname: Boucher
authors.affiliation: In Vitro Molecular Toxicology Laboratory, Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Boudreau
authors.affiliation: In Vitro Molecular Toxicology Laboratory, Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Atlas