title: Comparative in vivo and in vitro analysis of possible estrogenic effects of perfluorooctanoic acid.
abstract: Previous studies suggested that perfluorooctanoate (PFOA) could activate the estrogen receptor (ER). The present study examined the hypothesis that PFOA can activate ER using an in vivo uterotrophic assay in CD-1 mice and an in vitro reporter assay. Pre-pubertal female CD-1 mice fed an estrogen-free diet from postnatal day (PND)14 through weaning on PND18 were administered 0, 0.005, 0.01, 0.02, 0.05, 0.1, or 1mg/kg PFOA or 17β-estradiol (E2, 0.5mg/kg) from PND18-20. In contrast to E2, PFOA caused no changes in the relative uterine weight, the expression of ER target genes, or the morphology of the uterus/cervix and/or vagina on PND21. Treatment of a stable human cell line containing an ER-dependent luciferase reporter construct with a broad concentration range of PFOA caused no change in ER-dependent luciferase activity; whereas E2 caused a marked increase of ER-dependent luciferase activity. These data indicate that PFOA does not activate mouse or human ER.
authors.affiliation: Department of Veterinary and Biomedical Sciences and The Center of Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Pei-Li
authors.initials: PL
authors.lastname: Yao
authors.affiliation: Medical Department, 3 M Company, St. Paul, MN 55144, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Ehresman
authors.affiliation: Haskell Global Centers for Health and Environmental Sciences, Newark, DE 19701, USA.
authors.forename: Jessica M Caverly
authors.initials: JM
authors.lastname: Rae
authors.affiliation: Medical Department, 3 M Company, St. Paul, MN 55144, USA.
authors.forename: Shu-Ching
authors.initials: SC
authors.lastname: Chang
authors.affiliation: Haskell Global Centers for Health and Environmental Sciences, Newark, DE 19701, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Frame
authors.affiliation: Medical Department, 3 M Company, St. Paul, MN 55144, USA.
authors.forename: John L
authors.initials: JL
authors.lastname: Butenhoff
authors.affiliation: Consultant to DuPont Company, Wilmington, DE 19805, USA.
authors.forename: Gerald L
authors.initials: GL
authors.lastname: Kennedy
authors.affiliation: Department of Veterinary and Biomedical Sciences and The Center of Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, PA 16802, USA. Electronic address: jmp21@psu.edu.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Peters
mesh_terms: D000818:Animals; D002210:Caprylates / Q000633:toxicity*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004785:Environmental Pollutants / Q000633:toxicity*; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D005466:Fluorocarbons / Q000633:toxicity*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D051379:Mice; D009929:Organ Size; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D020218:Response Elements; D014162:Transfection; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014621:Vagina / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D002210:Caprylates; C506487:ESR1 protein, human; D004785:Environmental Pollutants; D047628:Estrogen Receptor alpha; D004967:Estrogens; D005466:Fluorocarbons; D011960:Receptors, Estrogen; D004958:Estradiol; C023036:perfluorooctanoic acid
keywords: Estrogen receptor; Perfluorooctanoate; Uterus