AI Article Synopsis
- Thyroid hormone carrier proteins are crucial for distributing thyroid hormones to tissues and regulating their balance in the blood.
- Interference with these carrier proteins could disrupt the thyroid system, prompting the need for more data on chemicals that impact them.
- A fluorescence-based screening assay tested over 1,400 chemicals, identifying 714 that significantly affected binding and narrowing down to 141 that showed potential for disrupting thyroid hormone balance, aiding future testing and data prediction efforts.
Article Abstract
Thyroid hormone (TH) carrier proteins play an important role in distributing TH to target tissue as well as maintaining the balance of free versus bound TH in the blood. Interference with the TH carrier proteins has been identified as a potential mechanism of thyroid system disruption. To address the lack of data regarding chemicals binding to these carrier proteins and displacing TH, a fluorescence-based screening assay was utilized to screen over 1,400 chemicals from the U.S. EPA's ToxCast phase1_v2, phase 2, and e1k libraries for competitive binding to one of the carrier proteins, thyroxine-binding globulin. Initial screening at a single high concentration of 100 μM identified 714 chemicals that decreased signal of the bound fluorescent ligand by 20% or higher. Of these, 297 produced 50% or greater reduction in fluorescence and were further tested in concentration-response (0.004 to 150 μM) to determine relative potency. Ten chemicals were found to have EC50 values <1 μM, 63 < 10 μM, and 141 chemicals between 10 and 100 μM. Utilization of this assay contributes to expanding the number of assays available for identifying chemicals with the potential to disrupt TH homeostasis. These results support ranking and prioritization of chemicals to be tested to aid in the development of a framework for predicting effects from high-throughput data.
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| http://dx.doi.org/10.1021/acs.chemrestox.4c00183 | DOI Listing |
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