Change search
ReferencesLink to record
Permanent link

Direct link
Competitive Binding of Poly- and Perfluorinated Compounds to the Thyroid Hormone Transport Protein Transthyretin
Umeå University, Faculty of Science and Technology, Chemistry.
Show others and affiliations
2009 (English)In: Toxicological sciences : an official journal of the Society of Toxicology, ISSN 1096-0929, Vol. 109, no 2, 206-16 p.Article in journal (Refereed) Published
Abstract [en]

Due to their unique surfactant properties, poly- and perfluorinated compounds (PFCs) have been extensively used, and can be found all over the environment.. Concern about their environmental fate and toxicological properties have initiated several research projects. In the present study, we investigated if PFCs can compete with thyroxin (T4, i.e. the transport form of thyroid hormone) for binding to the human thyroid hormone transport protein transthyretin (TTR). Such competitive capacity may lead to decreased thyroid hormone levels as previously reported for animals exposed to PFCs.

Twenty four PFCs, together with six structurally similar natural fatty acids, were tested for binding capacity in a radioligand binding assay. The binding potency decreased in the order: PFHxS>PFOS/PFOA>PFHpA>L-PFOSi>PFNA, with TTR binding potencies 12.5-50 times lower than the natural ligand thyroxine (T4). Some lower molecular weight compounds with structural similarity to these PFCs were >100 times less potent than T4.

Simple descriptors based on the two dimensional molecular structures of the compounds were used to visualize the chemical variation and to model the structure-activity relationship for the competitive potencies of the TTR-binding compounds. The models indicated the dependence on molecular size and functional group(s), but demanded a more detailed description of the chemical properties and data for validation and further QSAR development.

Competitive binding of PFCs to TTR as observed for human TTR in the present study, may explain altered thyroid hormone levels described for PFC-exposed rats and monkeys. Median human blood levels of the most potent TTR-binding PFCs are 1-2 orders of magnitude lower than IC50-values determined in the present study. In addition, this study contributes to the understanding of the bioaccumulation of PFCs in man and possibly in other wildlife species.

Place, publisher, year, edition, pages
Oxford University Press of the Society of Toxicology , 2009. Vol. 109, no 2, 206-16 p.
Keyword [en]
Perfluorinated Compounds (PFCs), Thyroid hormone, Thyroxine (T4), Transthyretin (TTR) binding, Perfluorooctane sulfonate (PFOS), Endocrine disruption
URN: urn:nbn:se:umu:diva-21142DOI: 10.1093/toxsci/kfp055PubMedID: 19293372OAI: diva2:210656
Available from: 2009-04-03 Created: 2009-04-03 Last updated: 2010-01-15Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Andersson, Patrik L
By organisation

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 52 hits
ReferencesLink to record
Permanent link

Direct link