PNNL

Abstract

Polybrominated diphenyl ether (PBDE) flame retardants have been implicated as disruptors of the hypothalamic-pituitary-thyroid axis. Animals exposed to PBDEs can show reduced plasma thyroid hormone (TH), but it is not known whether PBDE exposure impacts TH-regulated pathways in target tissues. Objective: Here we examined the effects of dietary exposure to 2,2´,4,4´-tetrabromodiphenyl ether (PBDE 47) – commonly the most highly concentrated PBDE in human tissues – on plasma TH levels and on gene transcription for glycoprotein hormone (GPH) a-subunit and thyrotropin (TSH) ß-subunit in the pituitary gland, and for the autoinduced TH receptors a and ß in the brain and liver. Methods: Breeding pairs of adult fathead minnows (Pimephales promelas) were given dietary PBDE 47 at two doses (12.3 µg/pair/day or 2.4 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 expression for TSH ß-subunit (low dose only) in the pituitary gland. PBDE 47 exposure also elevated gene transcription for TH receptor a in the brain of females, and decreased mRNA for TH receptor ß in the brain of both sexes. In males, dietary PBDE 47 intake also decreased brain gene transcripts for basic transcription element-binding protein (BTEB), a TH-responsive transcription factor.