title: Thyroid disruption by Di-n-butyl phthalate (DBP) and mono-n-butyl phthalate (MBP) in Xenopus laevis.
abstract: BACKGROUND
  Di-n-butyl phthalate (DBP), a chemical widely used in many consumer products, is estrogenic and capable of producing seriously reproductive and developmental effects in laboratory animals. However, recent in vitro studies have shown that DBP and mono-n-butyl phthalate (MBP), the major metabolite of DBP, possessed thyroid hormone receptor (TR) antagonist activity. It is therefore important to consider DBP and MBP that may interfere with thyroid hormone system.
  
  
  RESULTS
  Nieuwkoop and Faber stage 51 Xenopus laevis were exposed to DBP and MBP (2, 10 or 15 mg/L) separately for 21 days. The two test chemicals decelerated spontaneous metamorphosis in X. laevis at concentrations of 10 and 15 mg/L. Moreover, MBP seemed to possess stronger activity. The effects of DBP and MBP on inducing changes of expression of selected thyroid hormone response genes: thyroid hormone receptor-beta (TRβ), retinoid X receptor gamma (RXRγ), alpha and beta subunits of thyroid-stimulating hormone (TSHα and TSHβ) were detected by qPCR at all concentrations of the compounds. Using mammalian two-hybrid assay in vitro, we found that DBP and MBP enhanced the interactions between co-repressor SMRT (silencing mediator for retinoid and thyroid hormone receptors) and TR in a dose-dependent manner, and MBP displayed more markedly. In addition, MBP at low concentrations (2 and 10 mg/L) caused aberrant methylation of TRβ in head tissue.
  
  
  CONCLUSIONS
  The current findings highlight potential disruption of thyroid signalling by DBP and MBP and provide data for human risk assessment.
authors.affiliation: The Center for Disease Control and Prevention of Suzhou Industrial Park, Suzhou, China.
authors.forename: Ouxi
authors.initials: O
authors.lastname: Shen
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Guizhen
authors.initials: G
authors.lastname: Du
authors.forename: Renping
authors.initials: R
authors.lastname: Liu
authors.forename: Lugang
authors.initials: L
authors.lastname: Yu
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.forename: Xiumei
authors.initials: X
authors.lastname: Han
authors.forename: Yi
authors.initials: Y
authors.lastname: Jiang
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.forename: Ling
authors.initials: L
authors.lastname: Song
authors.forename: Yankai
authors.initials: Y
authors.lastname: Xia
authors.forename: Shoulin
authors.initials: S
authors.lastname: Wang
authors.forename: Xinru
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D003993:Dibutyl Phthalate / Q000494:pharmacology*; D010795:Phthalic Acids / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D011988:Receptors, Thyroid Hormone / Q000037:antagonists & inhibitors; D047491:Retinoid X Receptor gamma / Q000235:genetics / Q000378:metabolism; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism*; D037042:Thyroid Hormone Receptors beta / Q000235:genetics / Q000378:metabolism; D013972:Thyrotropin / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D010795:Phthalic Acids; D011988:Receptors, Thyroid Hormone; D047491:Retinoid X Receptor gamma; D037042:Thyroid Hormone Receptors beta; D003993:Dibutyl Phthalate; D013972:Thyrotropin; C028577:monobutyl phthalate