Development and Characterization of a Human Reporter Cell Line for the Assessment of Thyroid Receptor Transcriptional Activity: A Case of Organotin Endocrine Disruptors
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- Keywords
- cell line, luciferase reporter assay, organic tin compounds, thyroid hormone, thyroid receptor,
- MeSH
- Transcriptional Activation drug effects MeSH
- Cell Line drug effects metabolism MeSH
- Endocrine Disruptors pharmacology MeSH
- Humans MeSH
- Promoter Regions, Genetic drug effects MeSH
- Receptors, Thyroid Hormone genetics metabolism MeSH
- Genes, Reporter drug effects MeSH
- Transfection MeSH
- Triiodothyronine metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Endocrine Disruptors MeSH
- Receptors, Thyroid Hormone MeSH
- Triiodothyronine MeSH
We developed and characterized the human luciferase reporter cell line PZ-TR for the assessment of thyroid receptor (TR) transcriptional activity. Triiodothyronine (T3) induced luciferase activity in a dose-dependent manner, and the sensitivity of assay allowed for the detection of nanomolar T3 concentrations. The luciferase activity was induced by a maximum of (2.42 ± 0.14)-(2.73 ± 0.23)-fold after 24 h of exposure to 10 nM T3. We did not observe a nonspecific induction of luciferase activity by other steroid hormones and VDR ligands, with the exception of partial activation by retinoic acids. Cryopreservation of PZ-TR cells did not influence their functionality, responsivity to T3, or cell morphology, even after long-term cultivation. PZ-TR cells were used to evaluate the effects of organic tin compounds on TR. We found that the tributyltin and triphenyltin derivatives induced luciferase activity and that application of organotins in combination with T3 enhanced the effect of T3. These findings indicate that organic tin compounds have potential to interfere with TR-mediated regulation of gene expression and influence the physiological activity of thyroid hormones.
References provided by Crossref.org
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