pubmed.ncbi.nlm.nih.gov

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 - PubMed

. 2008 Dec;116(12):1694-9.

doi: 10.1289/ehp.11570. Epub 2008 Aug 1.

Affiliations

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

Sean C Lema et al. Environ Health Perspect. 2008 Dec.

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 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.

Keywords: PBDE-47; basic transcription element-binding protein; brain; endocrine disruption; polybrominated diphenyl ethers; thyroid hormone; thyroid hormone receptor; thyroid-stimulating hormone; thyrotropin.

PubMed Disclaimer

Figures

Figure 1
Figure 1

Exposure to PBDE-47 depressed circulating concentrations of total T4 in males and females (A), but had no effect on total T3 in males (B). *p < 0.05 compared with control.

Figure 2
Figure 2

Dietary exposure to PBDE-47 altered relative transcripts levels for TSHβ (A) and GPHα (B) in the pituitary gland. Transcript levels are expressed relative to template RNA levels. *p < 0.05 compared with control.

Figure 3
Figure 3

Dietary PBDE-47 exposure elevated mRNA levels for TRα in females (A), and reduced mRNA levels for TRβ in both sexes (B). PBDE-47 exposure also reduced gene transcripts for BTEB in the brain of male, but not female, minnows (C). Transcript levels are normalized to 18S. *p < 0.05 compared to control.

Similar articles

Cited by

References

    1. Adolf B, Chapouton P, Lam CS, Topp S, Tannhäuser B, Strähle U, et al. Conserved and acquired features of adult neurogenesis in the zebrafish telencephalon. Dev Biol. 2006;295:278–293. - PubMed
    1. Ankley GT, Villeneuve DL. The fathead minnow in aquatic toxicology: past, present and future. Aquat Toxicol. 2006;78:91–102. - PubMed
    1. Bagamasbad P, Howdeshell KL, Sachs LM, Demeneix BA, Denver RJ. A role for basic transcription element-binding protein 1 (BTEB 1) in the autoinduction of thyroid hormone receptor β. J Biol Chem. 2008;283:2275–2285. - PubMed
    1. Birnbaum LS, Staskal DF. Brominated flame retardants: cause for concern? Environ Health Perspect. 2004;112:9–17. - PMC - PubMed
    1. Boas M, Feldt-Rasmussen U, Skakkebæk NE, Main KM. Environmental chemicals and thyroid function. Eur J Endocrinol. 2006;154:599–611. - PubMed

Publication types

MeSH terms

Substances