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Thyroxine replacement modifies changes in deiodinase and thyroid hormone transporter expression induced by subclinical hypothyroidism in rats

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Abstract

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.

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Acknowledgments

We would like to thank the Fundação Carlos Chagas, Filho de Amparo à Pesquisa do Estado de São Paulo (FAPESP), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Capes) for financial support and R2G English Editing Services (São Paulo, SP, Brazil) for reviewing and editing the manuscript.

Funding

This project was funded by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) to Janaina Sena de Souza (FAPESP #2017/07053-3 and #2018/22763-0) and to Gisele Giannocco (FAPESP #2017/23169-1) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Capes) for the fellowship granted to Kellen Carneiro Oliveira and Rodrigo Rodrigues da Conceição.

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Correspondence to Rodrigo Rodrigues da Conceição or Gisele Giannocco.

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The authors declare that they have no conflict of interest.

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This investigation was carried out in accordance with the “Guide for the Care and Use of Laboratory Animals” published by the US National Institutes of Health (NIH Publication No.85-23, revised 1996) and was approved by the institutional animal welfare committee in consonance with pertinent Brazilian legislation under Protocols number: 078, book 02.

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Oliveira, K.C., Laureano-Melo, R., da Conceição, R.R. et al. Thyroxine replacement modifies changes in deiodinase and thyroid hormone transporter expression induced by subclinical hypothyroidism in rats. Hormones 20, 101–110 (2021). https://doi.org/10.1007/s42000-020-00247-1

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  • DOI: https://doi.org/10.1007/s42000-020-00247-1

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