title: Bisphenol A exposure is associated with in vivo estrogenic gene expression in adults.
abstract: BACKGROUND
  Bisphenol A (BPA) is a synthetic estrogen commonly used in polycarbonate plastic and resin-lined food and beverage containers. Exposure of animal and cell models to doses of BPA below the recommended tolerable daily intake (TDI) of 50 μg/kg/day have been shown to alter specific estrogen-responsive gene expression, but this has not previously been shown in humans.
  
  
  OBJECTIVE
  We investigated associations between BPA exposure and in vivo estrogenic gene expression in humans.
  
  
  METHODS
  We studied 96 adult men from the InCHIANTI population study and examined in vivo expression of six estrogen receptor, estrogen-related receptor, and androgen receptor genes in peripheral blood leukocytes.
  
  
  RESULTS
  The geometric mean urinary BPA concentration was 3.65 ng/mL [95% confidence interval (CI): 3.13, 4.28], giving an estimated mean excretion of 5.84 μg/day (95% CI: 5.00, 6.85), significantly below the current TDI. In age-adjusted models, there were positive associations between higher BPA concentrations and higher ESR2 [estrogen receptor 2 (ER beta)] expression (unstandardized linear regression coefficient = 0.1804; 95% CI: 0.0388, 0.3221; p = 0.013) and ESRRA (estrogen related receptor alpha) expression (coefficient = 0.1718; 95% CI: 0.0213, 0.3223; p = 0.026): These associations were little changed after adjusting for potential confounders, including obesity, serum lipid concentrations, and white cell subtype percentages. Upper-tertile BPA excretors (urinary BPA > 4.6 ng/mL) had 65% higher mean ESR2 expression than did lower-tertile BPA excretors (0-2.4 ng/mL).
  
  
  CONCLUSIONS
  Because activation of nuclear-receptor-mediated pathways by BPA is consistently found in laboratory studies, such activation in humans provides evidence that BPA is likely to function as a xenoestrogen in this sample of adults.
authors.affiliation: Epidemiology and Public Health, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Melzer
authors.forename: Lorna
authors.initials: L
authors.lastname: Harries
authors.forename: Riccardo
authors.initials: R
authors.lastname: Cipelli
authors.forename: William
authors.initials: W
authors.lastname: Henley
authors.forename: Cathryn
authors.initials: C
authors.lastname: Money
authors.forename: Paul
authors.initials: P
authors.lastname: McCormack
authors.forename: Anita
authors.initials: A
authors.lastname: Young
authors.forename: Jack
authors.initials: J
authors.lastname: Guralnik
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: Stefania
authors.initials: S
authors.lastname: Bandinelli
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Corsi
authors.forename: Tamara
authors.initials: T
authors.lastname: Galloway
mesh_terms: D000328:Adult; D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors / Q000633:toxicity* / Q000652:urine; D004781:Environmental Exposure; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007558:Italy; D007962:Leukocytes / Q000378:metabolism*; D016014:Linear Models; D010636:Phenols / Q000633:toxicity* / Q000652:urine; D060888:Real-Time Polymerase Chain Reaction; D011944:Receptors, Androgen / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D010636:Phenols; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; C006780:bisphenol A; D000098826:Bisphenol A Compounds