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Synthesis and Regulation of Thyroid Hormones

Synthesis and Regulation of Thyroid Hormones

Low blood levels of the thyroid hormones — triiodothyronine (T3) and thyroxine (T4) — signal the hypothalamus to release the thyrotropin-releasing hormone (TRH). TRH then reaches the pituitary gland and stimulates the release of thyroid-stimulating hormone(TSH) into the bloodstream.
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The...

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Author Spotlight: In Vivo Assessment of Thyroid Hormone Disruption Using the THAI Mouse Model

Author Spotlight: In Vivo Assessment of Thyroid Hormone Disruption Using the THAI Mouse Model

Published on: October 6, 2023

A rodent thyroid-liver chip to capture thyroid toxicity on organ function level.

Diana Karwelat¹, Julia Kühnlenz^2,3, Thomas Steger-Hartmann¹

¹Pharmaceuticals Division, Investigational Toxicology, Bayer AG, Germany.

|July 6, 2022

Summary

A new rat thyroid-liver chip model can identify chemical effects on thyroid function in vitro. This advanced model aids in assessing thyroid-disrupting chemicals and improving human safety risk assessments.

Keywords:

T4 glucuronidation endocrine disruption liver enzyme activation organs-on-a-chip thyroid hormone inhibition

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Last Updated: Sep 5, 2025

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Published on: October 6, 2023

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro

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Published on: January 31, 2022

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment

Published on: December 3, 2020

Area of Science:

Toxicology and Endocrine Disruption
In Vitro Modeling
Environmental Health

Background:

Environmental chemicals can disrupt endocrine function, posing risks to human safety.
Rats are sensitive to thyroid disruption, but species differences create uncertainty in human risk assessments.
In vitro models are needed to identify mechanisms of thyroid perturbation across species.

Purpose of the Study:

To develop a rat thyroid-liver chip for simultaneous in vitro identification of direct and indirect thyroid perturbation.
To assess the model's ability to maintain tissue-specific phenotypes and functions.
To evaluate the model's proficiency in detecting thyroid-disrupting chemicals.

Main Methods:

A microfluidic chip combining primary rat thyroid follicles and liver 3D spheroids was created.
The model's tissue-specific phenotype, thyroid hormone secretion, and liver functions were maintained for 21 days.
Reference chemicals were used to test the model's ability to detect thyroid perturbation mechanisms.

Main Results:

The rat thyroid-liver chip maintained follicular architecture, thyroid hormone (T4) secretion, and liver functions (albumin, urea, T4-glucuronide formation).
The model successfully detected direct thyroid perturbation via decreased T4 secretion.
Indirect (liver-mediated) thyroid perturbation was identified through increased T4-glucuronide formation.

Conclusions:

The rat thyroid-liver chip is a functional in vitro model for assessing thyroid-disrupting chemicals.
This model supports mechanistic identification of direct and indirect thyroid perturbation.
The chip, alongside a human counterpart, can improve species-specific extrapolation for human safety risk assessment and advance the 3R principles.