title: Development of phenotypic and transcriptional biomarkers to evaluate relative activity of potentially estrogenic chemicals in ovariectomized mice.
abstract: BACKGROUND
  Concerns regarding potential endocrine-disrupting chemicals (EDCs) have led to a need for methods to evaluate candidate estrogenic chemicals. Our previous evaluations of two such EDCs revealed a response similar to that of estradiol (E2) at 2 hr, but a less robust response at 24 hr, similar to the short-acting estrogen estriol (E3).
  
  
  OBJECTIVE
  Microarray analysis using tools to recognize patterns of response have been utilized in the cancer field to develop biomarker panels of transcripts for diagnosis and selection of treatments most likely to be effective. Biological effects elicited by long- versus short-acting estrogens greatly affect the risks associated with exposures; therefore, we sought to develop tools to predict the ability of chemicals to maintain estrogenic responses.
  
  
  METHODS
  We used biological end points in uterine tissue and a signature pattern-recognizing tool that identified coexpressed transcripts to develop and test a panel of transcripts in order to classify potentially estrogenic compounds using an in vivo system. The end points used are relevant to uterine tissue, but the resulting classification of the compounds is important for other sensitive tissues and species.
  
  
  RESULTS
  We evaluated biological and transcriptional end points with proven short- and long-acting estrogens and verified the use of our approach using a phytoestrogen. With our model, we were able to classify the diarylheptanoid D3 as a short-acting estrogen.
  
  
  CONCLUSIONS
  We have developed a panel of transcripts as biomarkers which, together with biological end points, might be used to screen and evaluate potentially estrogenic chemicals and infer mode of activity.
authors.affiliation: Receptor Biology, Reproductive and Developmental Biology Laboratory.
authors.forename: Sylvia C
authors.initials: SC
authors.lastname: Hewitt
authors.forename: Wipawee
authors.initials: W
authors.lastname: Winuthayanon
authors.forename: Brianna
authors.initials: B
authors.lastname: Pockette
authors.forename: Robnet T
authors.initials: RT
authors.lastname: Kerns
authors.forename: Julie F
authors.initials: JF
authors.lastname: Foley
authors.forename: Norris
authors.initials: N
authors.lastname: Flagler
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ney
authors.forename: Apichart
authors.initials: A
authors.lastname: Suksamrarn
authors.forename: Pawinee
authors.initials: P
authors.lastname: Piyachaturawat
authors.forename: Pierre R
authors.initials: PR
authors.lastname: Bushel
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Korach
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D036381:Diarylheptanoids / Q000633:toxicity; D052244:Endocrine Disruptors / Q000633:toxicity*; D004967:Estrogens / Q000633:toxicity; D005260:Female; D020869:Gene Expression Profiling; D051379:Mice; D008810:Mice, Inbred C57BL; D010052:Ovariectomy; D048789:Phytoestrogens / Q000633:toxicity; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D036381:Diarylheptanoids; D052244:Endocrine Disruptors; D004967:Estrogens; D048789:Phytoestrogens