Dietary exposure to 2,2',4,4'-tetrabromodiphenyl ether (PBDE-47) alters thyroid status and thyroid hormone-regulated gene transcription in the pituitary and brain.
BACKGROUND
Polybrominated diphenyl ether (PBDE) flame retardants have been implicated as disruptors of the hypothalamic-pituitary-thyroid axis. Animals exposed to PBDEs may show reduced plasma thyroid hormone (TH), but it is not known whether PBDEs impact TH-regulated pathways in target tissues.


OBJECTIVE
We examined the effects of dietary exposure to 2,2',4,4'-tetrabromodiphenyl ether (PBDE-47)-commonly the highest concentrated PBDE in human tissues-on plasma TH levels and on gene transcripts for glycoprotein hormone alpha-subunit (GPHalpha) and thyrotropin beta-subunit (TSHbeta) in the pituitary gland, the auto-induced TH receptors alpha and beta in the brain and liver, and the TH-responsive transcription factor basic transcription element-binding protein (BTEB) in the brain.


METHODS
Breeding pairs of adult fathead minnows (Pimephales promelas) were given dietary PBDE-47 at two doses (2.4 microg/pair/day or 12.3 microg/pair/day) for 21 days.


RESULTS
Minnows exposed to PBDE-47 had depressed plasma thyroxine (T(4)), but not 3,5,3'-triiodothyronine (T(3)). This decline in T(4) was accompanied by elevated mRNA levels for TStHbeta (low dose only) in the pituitary. PBDE-47 intake elevated transcript for TH receptor alpha in the brain of females and decreased mRNA for TH receptor beta in the brain of both sexes, without altering these transcripts in the liver. In males, PBDE-47 exposure also reduced brain transcripts for BTEB.


CONCLUSIONS
Our results indicate that dietary exposure to PBDE-47 alters TH signaling at multiple levels of the hypothalamic-pituitary-thyroid axis and provide evidence that TH-responsive pathways in the brain may be particularly sensitive to disruption by PBDE flame retardants.
Lema
Sean C
SC
Physiology Program, Northwest Fisheries Science Center, National Oceanic and Atmospheric Administration, Seattle, Washington, USA.
Dickey
Jon T
JT
Schultz
Irvin R
IR
Swanson
Penny
P
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003530:Cyprinidae; D004032:Diet; D005260:Female; D055768:Halogenated Diphenyl Ethers / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D008099:Liver / Q000378:metabolism; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism; D011075:Polybrominated Biphenyls; D012333:RNA, Messenger / Q000235:genetics; D011863:Radioimmunoassay; D011988:Receptors, Thyroid Hormone / Q000235:genetics; D013961:Thyroid Gland / Q000187:drug effects* / Q000502:physiology; D013963:Thyroid Hormones / Q000502:physiology*; D014018:Tissue Distribution; D014158:Transcription, Genetic / Q000502:physiology*
D055768:Halogenated Diphenyl Ethers; D011075:Polybrominated Biphenyls; D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones; C511295:2,2',4,4'-tetrabromodiphenyl ether