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 (GPH alpha) and thyrotropin beta-subunit (TSH beta) in the pituitary gland, the autoinduced 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 mu g/pair/day or 12.3 mu g/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 TSH beta (low dose only) in the pituitary. PBDE-47 intake elevated transcript for TH receptor a 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.