Dechloranes exhibit binding potency and activity to thyroid hormone receptors

Area of Science:

• Environmental Chemistry
• Toxicology
• Endocrinology

Background:

• Dechloranes are halogenated flame retardants.
• Dechlorane Plus (DP) has demonstrated thyroid-interfering effects in previous studies.
• The specific mechanisms by which dechloranes affect thyroid function are not fully understood.

Purpose of the Study:

• To investigate the potential of four dechloranes (DP, Dec 602, Dec 603, Dec 604) to interfere with thyroid function.
• To examine the interaction of these dechloranes with thyroid hormone receptors (TRs), specifically TRα and TRβ.
• To determine the antagonistic or agonistic activity of dechloranes on TR signaling pathways.

Main Methods:

• Fluorescence competitive binding assays were used to determine the binding affinities of dechloranes to TRα and TRβ.
• Relative potency (RP) values were calculated to quantify binding affinity.
• TRs-mediated luciferase reporter gene assays and T-screen assays were employed to assess the cellular activity of dechloranes on TRs.

Main Results:

• All four tested dechloranes (DP, Dec 602, Dec 603, Dec 604) demonstrated the ability to bind to both TRα and TRβ.
• Dechloranes showed a higher binding affinity for TRβ compared to TRα.
• The compounds exhibited antagonistic activity against TRs in cellular assays, indicating they block normal thyroid hormone signaling.

Conclusions:

• Dechloranes can interfere with thyroid function by binding to thyroid hormone receptors and acting as antagonists.
• The observed selectivity for TRβ suggests tissue-specific effects of dechloranes.
• The findings highlight potential health risks associated with dechlorane exposure, particularly for highly exposed populations.