title: Differential Activation of a Mouse Estrogen Receptor β Isoform (mERβ2) with Endocrine-Disrupting Chemicals (EDCs).
abstract: Endocrine-disrupting chemicals (EDCs) are suspected of altering estrogenic signaling through estrogen receptor (ER) α or β (mERβ1 in mice). Several EDC effects have been reported in animal studies and extrapolated to human studies. Unlike humans, rodents express a novel isoform of ERβ (mERβ2) with a modified ligand-binding domain sequence. EDC activity through this isoform remains uncharacterized.
  
  
  
  We identified the expression pattern of mERβ2 in mouse tissues and assessed the estrogenic activity of EDCs through mERβ2.
  
  
  
  mERβ2 mRNA expression was measured in mouse tissues. HepG2 cells were used to assess the transactivation activity of mERβ isoforms with EDCs and ER co-activators. 293A cells transiently transfected with mER isoforms were used to detect EDC-mediated changes in endogenous ER target gene expression.
  
  
  
  Expression of mERβ2 mRNA was detected in mouse reproductive tissues (ovary, testis, and prostate) and lung and colon tissues from both female and male mice. Five (E2, DES, DPN, BPAF, Coum, 1-BP) of 16 compounds tested by reporter assay had estrogenic activity through mERβ2. mERβ2 had a compound-specific negative effect on ERβ/ligand-mediated activity and ER target genes when co-expressed with mERβ1. mERβ2 recruited coactivators SRC2 or SRC3 in the presence of EDCs, but showed less recruitment than mERβ1.
  
  
  
  mERβ2 showed weaker estrogenic activity than mERβ1 in ourin vitrosystem, and can dampen mERβ1 activity.In vivomodels of EDC activity and ER-mediated toxicity should consider the role of mERβ2, as rodent tissue responses involving mERβ2 may not be reproduced in human biology.
authors.affiliation: Receptor Biology Section, Reproductive and Developmental Biology Laboratory, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA.
authors.forename: Lauren J
authors.initials: LJ
authors.lastname: Donoghue
authors.forename: Thomas I
authors.initials: TI
authors.lastname: Neufeld
authors.forename: Yin
authors.initials: Y
authors.lastname: Li
authors.forename: Yukitomo
authors.initials: Y
authors.lastname: Arao
authors.forename: Laurel A
authors.initials: LA
authors.lastname: Coons
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Korach
mesh_terms: D000818:Animals; D052244:Endocrine Disruptors / Q000633:toxicity*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D052244:Endocrine Disruptors; D047629:Estrogen Receptor beta; D012333:RNA, Messenger