PMID- 18978342
OWN - NLM
STAT- MEDLINE
DCOM- 20090807
LR  - 20240109
IS  - 1096-0929 (Electronic)
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 107
IP  - 1
DP  - 2009 Jan
TI  - Effects of perinatal PBDE exposure on hepatic phase I, phase II, phase III, and 
      deiodinase 1 gene expression involved in thyroid hormone metabolism in male rat 
      pups.
PG  - 27-39
LID - 10.1093/toxsci/kfn230 [doi]
AB  - Previous studies demonstrated that perinatal exposure to polybrominated diphenyl 
      ethers (PBDEs), a major class of brominated flame retardants, may affect thyroid 
      hormone (TH) concentrations by inducing hepatic 
      uridinediphosphate-glucoronosyltransferases (UGTs). This study further examines 
      effects of the commercial penta mixture, DE-71, on genes related to TH metabolism 
      at different developmental time points in male rats. DE-71 is predominately 
      composed of PBDE congeners 47, 99, 100, 153, 154 with low levels of brominated 
      dioxin and dibenzofuran contaminants. Pregnant Long-Evans rats were orally 
      administered 1.7 (low), 10.2 (mid), or 30.6 (high) mg/kg/day of DE-71 in corn oil 
      from gestational day (GD) 6 to postnatal day (PND) 21. Serum and liver were 
      collected from male pups at PND 4, 21, and 60. Total serum thyroxine (T(4)) 
      decreased to 57% (mid) and 51% (high) on PND 4, and 46% (mid) dose and 25% (high) 
      on PND 21. Cyp1a1, Cyp2b1/2, and Cyp3a1 enzyme and mRNA expression, regulated by 
      aryl hydrocarbon receptor, constitutive androstane receptor, and pregnane 
      xenobiotic receptor, respectively, increased in a dose-dependent manner. UGT-T(4) 
      enzymatic activity significantly increased, whereas age and dose-dependent 
      effects were observed for Ugt1a6, 1a7, and 2b mRNA. Sult1b1 mRNA expression 
      increased, whereas that of transthyretin (Ttr) decreased as did both the 
      deiodinase I (D1) enzyme activity and mRNA expression. Hepatic efflux 
      transporters Mdr1 (multidrug resistance), Mrp2 (multidrug resistance-associated 
      protein), and Mrp3 and influx transporter Oatp1a4 mRNA expression increased. In 
      this study the most sensitive responses to PBDEs following DE-71 exposure were 
      CYP2B and D1 activities and Cyb2b1/2, d1, Mdr1, Mrp2, and Mrp3 gene expression. 
      All responses were reversible by PND 60. In conclusion, deiodination, active 
      transport, and sulfation, in addition to glucuronidation, may be involved in 
      disruption of TH homeostasis due to perinatal exposure to DE-71 in male rat 
      offspring.
FAU - Szabo, David T
AU  - Szabo DT
AD  - University of North Carolina Curriculum in Toxicology, United States 
      Environmental Protection Agency, Research Triangle Park, North Carolina 27711, 
      USA.
FAU - Richardson, Vicki M
AU  - Richardson VM
FAU - Ross, David G
AU  - Ross DG
FAU - Diliberto, Janet J
AU  - Diliberto JJ
FAU - Kodavanti, Prasada R S
AU  - Kodavanti PR
FAU - Birnbaum, Linda S
AU  - Birnbaum LS
LA  - eng
GR  - T32 ES007126/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20081031
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Flame Retardants)
RN  - 0 (Halogenated Diphenyl Ethers)
RN  - 06LU7C9H1V (Triiodothyronine)
RN  - 7REL09ZX35 (pentabromodiphenyl ether)
RN  - EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases)
RN  - EC 2.4.1.17 (Glucuronosyltransferase)
RN  - EC 2.8.2.- (Sulfotransferases)
RN  - Q51BO43MG4 (Thyroxine)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Animals, Newborn
MH  - Aryl Hydrocarbon Hydroxylases/genetics/*metabolism
MH  - Female
MH  - Flame Retardants/administration & dosage/toxicity
MH  - Gene Expression Regulation/drug effects
MH  - Gene Expression Regulation, Developmental/*drug effects
MH  - Glucuronosyltransferase/genetics/metabolism
MH  - Halogenated Diphenyl Ethers/administration & dosage/*toxicity
MH  - Male
MH  - Microsomes, Liver/chemistry
MH  - Pregnancy
MH  - Rats
MH  - Rats, Long-Evans
MH  - Sulfotransferases/genetics/metabolism
MH  - Thyroxine/*analysis/blood
MH  - Triiodothyronine/analysis/blood
PMC - PMC2638650
EDAT- 2008/11/04 09:00
MHDA- 2009/08/08 09:00
PMCR- 2010/01/01
CRDT- 2008/11/04 09:00
PHST- 2008/11/04 09:00 [entrez]
PHST- 2008/11/04 09:00 [pubmed]
PHST- 2009/08/08 09:00 [medline]
PHST- 2010/01/01 00:00 [pmc-release]
AID - kfn230 [pii]
AID - 10.1093/toxsci/kfn230 [doi]
PST - ppublish
SO  - Toxicol Sci. 2009 Jan;107(1):27-39. doi: 10.1093/toxsci/kfn230. Epub 2008 Oct 31.