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

Abstract

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 a-subunit (GPHa) and thyrotropin β-subunit (TSHβ) in the pituitary gland, the autoinduced TH receptors α and β 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 μg/pair/day or 12.3 μg/pair/day) for 21 days. Results: Minnows exposed to PBDE-47 had depressed plasma thyroxine (T4), but not 3,5,3′-triiodothyronine (T3). This decline in T4 was accompanied by elevated mRNA levels for TSHβ (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 β 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.