title: Placenta expressing the greatest quantity of bisphenol A receptor ERR{gamma} among the human reproductive tissues: Predominant expression of type-1 ERRgamma isoform.
abstract: Estrogen-related receptor gamma (ERRgamma), one of the 48 human nuclear receptors, has a fully active conformation with no ligand. We recently demonstrated that ERRgamma binds strongly bisphenol A (BPA), one of the nastiest endocrine disruptors, and thus retaining ERRgamma's high basal constitutive activity. A report that BPA accumulates in the human maternal-fetal placental unit has led us to hypothesize that a large amount of ERRgamma might exist in the human placenta. Here we report evidence that placenta indeed expresses ERRgamma exceptionally strongly. We first ascertained the presence of nine different ERRgamma mRNA variants and the resulting three ERRgamma protein isoforms. By real-time PCR, we estimated the relative amount of ERRgamma mRNA using total RNA extracts from human reproductive tissues. Placenta was found to express ERRgamma extremely highly. Among the three ERRgamma protein isoforms, placenta exclusively expresses the type-1 isoform, which possesses additional 23-mer amino-acid residues at the N-terminus of the ordinary ERRgamma. This N-terminal elongation was found to elevate by approximately 50% the basal constitutive activity of ERRgamma, as evidenced in the luciferase reporter gene assay. The present results suggest that BPA accumulates in the placenta by binding to ERRgamma.
authors.affiliation: Department of Chemistry, The Research- Education Centre of Risk Science, Kyushu University, Fukuoka, Japan.
authors.forename: Yukimasa
authors.initials: Y
authors.lastname: Takeda
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Liu
authors.forename: Miho
authors.initials: M
authors.lastname: Sumiyoshi
authors.forename: Ayami
authors.initials: A
authors.lastname: Matsushima
authors.forename: Miki
authors.initials: M
authors.lastname: Shimohigashi
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Shimohigashi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001559:Benzhydryl Compounds; D001921:Brain / Q000196:embryology / Q000378:metabolism; D052244:Endocrine Disruptors / Q000378:metabolism*; D004968:Estrogens, Non-Steroidal / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007668:Kidney / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism; D010053:Ovary / Q000737:chemistry / Q000378:metabolism; D010179:Pancreas / Q000737:chemistry / Q000378:metabolism; D010636:Phenols / Q000378:metabolism*; D010920:Placenta / Q000737:chemistry / Q000378:metabolism*; D011467:Prostate / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000819:agonists / Q000737:chemistry / Q000378:metabolism*; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D013737:Testis / Q000737:chemistry / Q000378:metabolism; D014599:Uterus / Q000737:chemistry / Q000378:metabolism; D055815:Young Adult; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D004968:Estrogens, Non-Steroidal; D010636:Phenols; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D013629:Tamoxifen; C490917:ESRRG protein, human; C016601:afimoxifene; C006780:bisphenol A; D000098826:Bisphenol A Compounds