Identification of classifiers for increase or decrease of thyroid peroxidase activity in the FTC-238/hTPO recombinant...

Area of Science:

• Endocrinology
• Toxicology
• Molecular Biology

Background:

• Thyroid peroxidase (TPO) is crucial for thyroid hormone biosynthesis, catalyzing iodide organification.
• The traditional guaiacol assay for TPO activity is complex and time-consuming.
• TPO activity is a sensitive target for endocrine-disrupting chemicals.

Purpose of the Study:

• To develop a simplified, microarray-based method for detecting changes in TPO activity.
• To assess the utility of transcriptomic endpoints as enhancements to existing TPO assays.
• To identify gene expression signatures predictive of TPO activity modulation by toxicants.

Main Methods:

• Utilized human oligonucleotide microarrays to analyze gene expression profiles.
• Exposed FTC-238 human follicular thyroid carcinoma cells expressing human recombinant TPO to various TPO activity-disrupting agents.
• Identified gene expression classifiers to predict the impact of toxicants on TPO activity.

Main Results:

• Successfully identified 362 gene expression classifiers.
• These classifiers predicted the effect of toxicants on TPO activity with approximately 70% accuracy.
• Demonstrated that specific chemicals either decrease (e.g., benzophenone-2, PFOS) or increase (e.g., dibutyl phthalate, methylmercury) TPO activity.

Conclusions:

• The developed microarray method offers a simplified approach to assess TPO activity.
• Transcriptomic profiling can serve as a valuable tool for predicting chemical disruption of thyroid hormone production.
• The identified classifiers represent potential biomarkers for evaluating thyroid-disrupting chemicals.