In vivo Characterization of Endocrine Disrupting Chemical Effects via Thyroid Hormone Action Indicator Mouse

作者： Richárd Sinkó1,2, Petra Mohácsik1, Csaba Fekete*3, Balázs Gereben*1 1Laboratory of Molecular Cell Metabolism,Institute of Experimental Medicine, 2János Szentágothai PhD School of Neurosciences,Semmelweis University, 3Laboratory of Integrative Neuroendocrinology,Institute of Experimental Medicine

简介：

Overview

The Thyroid Hormone Action Indicator (THAI) mouse model was developed to enable tissue-specific quantification of local thyroid hormone action. This model is particularly useful for characterizing the effects of endocrine-disrupting chemicals on thyroid hormone economy through both ex vivo and in vivo methodologies.

Key Study Components

Area of Science

• Endocrinology
• Toxicology
• In vivo Imaging

Background

• Endocrine disruptors can interfere with thyroid hormone economy in mammals.
• Thyroid hormones are crucial regulators of biological functions.
• Existing screening methods for endocrine disruptors have limitations in assessing their tissue-specific effects in vivo.
• A need exists for test systems that can quantitatively measure local thyroid hormone action.

Purpose of Study

• Characterize thyroid hormone action in tissues using the THAI mouse model.
• Measure the tissue-specific effects of endocrine disruptors in vivo.
• Assess the impact of specific molecules and their metabolites on thyroid hormone economy.

Methods Used

• The THAI mouse model is used for in vivo imaging of thyroid hormone action.
• Animals are subjected to bioluminescent imaging to detect changes in local thyroid hormone activity.
• Luciferin is administered intraperitoneally for imaging assessment.
• Monitoring includes imaging time settings and analysis of specific regions of interest (ROIs).

Main Results

• In vivo imaging revealed higher basal luciferase signals in non-furred areas such as foot pads and tail.
• Significant thyroid hormone action was noted in the brown adipose tissue during cold stress.
• It was found that the treatment did not impact luciferase signals from certain areas.
• Imaging studies tracked the accumulation and clearance of the endocrine disruptor diclazuril over three weeks.

Conclusions

• The THAI model enables an in vivo understanding of thyroid hormone dynamics and its disruption by chemicals.
• This model facilitates the characterization of endocrine disruptors’ effects in a living organism, potentially reducing the number of animals needed for studies.
• Implications extend to a better understanding of thyroid hormone regulation and environmental pollutant impacts on mammalian physiology.

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