title: Endocrine disruption in human placenta: expression of the dioxin-inducible enzyme, CYP1A1, is correlated with that of thyroid hormone-regulated genes.
abstract: BACKGROUND
  Thyroid hormone (TH) is essential for normal development; therefore, disruption of TH action by a number of industrial chemicals is critical to identify. Several chemicals including polychlorinated biphenyls are metabolized by the dioxin-inducible enzyme CYP1A1; some of their metabolites can interact with the TH receptor. In animals, this mechanism is reflected by a strong correlation between the expression of CYP1A1 mRNA and TH-regulated mRNAs. If this mechanism occurs in humans, we expect that CYP1A1 expression will be positively correlated with the expression of genes regulated by TH.
  
  
  OBJECTIVE
  The objective of the study was to test the hypothesis that CYP1A1 mRNA expression is correlated with TH-regulated mRNAs in human placenta.
  
  
  METHODS
  One hundred sixty-four placental samples from pregnancies with no thyroid disease were obtained from the GESTE study (Sherbrooke, Québec, Canada). Maternal and cord blood TH levels were measured at birth. The mRNA levels of CYP1A1 and placental TH receptor targets [placental lactogen (PL) and GH-V] were quantitated by quantitative PCR.
  
  
  RESULTS
  CYP1A1 mRNA abundance varied 5-fold across 132 placental samples that had detectable CYP1A1 mRNA. CYP1A1 mRNA was positively correlated with PL (r = 0.64; P < .0001) and GH-V (P < .0001, r = 0.62) mRNA. PL and GH-V mRNA were correlated with each other (r = 0.95; P < .0001), suggesting a common activator. The mRNAs not regulated by TH were not correlated with CYP1A1 expression.
  
  
  CONCLUSIONS
  CYP1A1 mRNA expression is strongly associated with the expression of TH-regulated target gene mRNAs in human placenta, consistent with the endocrine-disrupting action of metabolites produced by CYP1A1.
authors.affiliation: Department of Biology (T.L.W., K.G., J.M.B., R.B., R.T.Z.), University of Massachusetts Amherst, Amherst, Massachusetts 01003; Department of Pediatrics (T.L.W.), Baystate Medical Center, Springfield, Massachusetts 01199; and Department of Pediatrics (N.A., L.T.), Faculty of Medicine, and Department of Medicine (M.-F.L.), Endocrinology Service, Faculty of Medicine, University of Sherbrooke, Sherbrooke, Qéubec, Canada J1H SN4.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Wadzinski
authors.forename: Katherine
authors.initials: K
authors.lastname: Geromini
authors.forename: Judy
authors.initials: J
authors.lastname: McKinley Brewer
authors.forename: Ruby
authors.initials: R
authors.lastname: Bansal
authors.forename: Nadia
authors.initials: N
authors.lastname: Abdelouahab
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Langlois
authors.forename: Larissa
authors.initials: L
authors.lastname: Takser
authors.forename: R Thomas
authors.initials: RT
authors.lastname: Zoeller
mesh_terms: D000328:Adult; D002460:Cell Line; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D004147:Dioxins; D052244:Endocrine Disruptors / Q000494:pharmacology*; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics* / Q000502:physiology*; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D010920:Placenta / Q000187:drug effects / Q000201:enzymology*; D010928:Placental Lactogen / Q000097:blood; D011247:Pregnancy; D012907:Smoking / Q000235:genetics; D013963:Thyroid Hormones / Q000378:metabolism / Q000502:physiology*
chemical_list: D004147:Dioxins; D052244:Endocrine Disruptors; D013963:Thyroid Hormones; D019382:Human Growth Hormone; D010928:Placental Lactogen; D019363:Cytochrome P-450 CYP1A1