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Updated: Dec 7, 2025
Author Spotlight: In Vivo Assessment of Thyroid Hormone Disruption Using the THAI Mouse Model
Published on: October 6, 2023
Thyroxine replacement modifies changes in deiodinase and thyroid hormone transporter expression induced by
Kelen Carneiro Oliveira1, Roberto Laureano-Melo2, Rodrigo Rodrigues da Conceição3
1Laboratório de Endocrinologia Molecular e Translacional- LEMT, Divisão de Endocrinologia, Departamento de Medicina, Universidade Federal de São Paulo (UNIFESP), Rua Pedro de Toledo, 669, Vila Clementino, São Paulo, SP, 04039032, Brazil.
Purpose:
The potential benefits of treating subclinical hypothyroidism (SCH) are unclear and still controversial. Thus, we surgically induced SCH in rats and evaluated the effects of thyroxine (T4) replacement on the gene expression levels of deiodinases and thyroid hormone (TH) transporters in different tissues.
Methods:
SCH was induced by hemithyroid electrocauterization. The control animals underwent the same surgical procedure but were not subjected to electrocauterization (sham). After 14 days, half of the SCH animals were treated with T4 (SCH + T4). At the end of the experimental protocol, all of the rats were euthanized, serum hormone concentrations were measured, and RNA analyses were performed on different tissues and organs.
Results:
Consistent with previous studies, we observed increased TSH levels, normal TH levels, and reduced hypothalamic TRH expression in the SCH group. Additionally, Dio2 mRNA expression was downregulated in the hippocampus and pituitary, and Dio1 was upregulated in the kidney and pituitary of the SCH animals. The changes in Dio3 expression were tissue-specific. Concerning TH transporters, Mct10 expression was upregulated in the pituitary, kidney, hypothalamus, and hippocampus, and Mct8 expression was downregulated in the kidney of the SCH group. Crym expression was upregulated in the kidney and pituitary. Notably, T4 replacement significantly attenuated serum TSH levels and reverted Dio1, Dio2, Mct10, and Crym expression in the pituitary, hippocampus, and kidney to levels that were similar to the sham group. Tissue-specific responses were also observed in the liver and hypothalamus.
Conclusion:
Our results indicate that treatment of SCH should be considered before the appearance of clinical symptoms of hypothyroidism.
Insights
Treating subclinical hypothyroidism (SCH) with thyroxine (T4) normalized gene expression of deiodinases and thyroid hormone transporters in rats. Early T4 treatment may prevent clinical symptoms of hypothyroidism.
Area of Science:
- Endocrinology
- Molecular Biology
- Animal Models
Background:
- Subclinical hypothyroidism (SCH) treatment remains controversial.
- Thyroid hormone (TH) deiodinases and transporters play crucial roles in TH metabolism and action.
- Understanding gene expression changes in SCH is vital for determining optimal treatment strategies.
Purpose of the Study:
- To investigate the effects of thyroxine (T4) replacement on deiodinase and TH transporter gene expression in a rat model of surgically induced SCH.
- To evaluate tissue-specific changes in gene expression in response to SCH and T4 treatment.
Main Methods:
- Subclinical hypothyroidism (SCH) was induced in rats via hemithyroid electrocauterization.
- Thyroxine (T4) replacement therapy was administered to a subset of SCH rats.
- Serum hormone levels and gene expression (deiodinases, TH transporters) were analyzed in various tissues.
Main Results:
- SCH rats exhibited altered expression of deiodinases (Dio1, Dio2, Dio3) and TH transporters (Mct10, Mct8, Crym) in a tissue-specific manner.
- T4 replacement therapy normalized TSH levels and reverted most altered gene expressions to sham levels.
- Significant changes were observed in the pituitary, hippocampus, kidney, liver, and hypothalamus.
Conclusions:
- Thyroxine (T4) replacement effectively modulates gene expression of deiodinases and TH transporters in SCH.
- These findings support considering T4 treatment for SCH before overt clinical symptoms manifest.
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