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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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Author(s):
Oliveira, Kelen Carneiro ; Laureano-Melo, Roberto ; da Conceicao, Rodrigo Rodrigues ; de Souza, Janaina Sena ; da Silva Cortes, Wellington ; Sato, Monica Akemi ; Chiamolera, Maria Izabel ; Maciel, Rui Monteiro ; Giannocco, Gisele
Total Authors: 9
Document type: Journal article
Source: HORMONES-INTERNATIONAL JOURNAL OF ENDOCRINOLOGY AND METABOLISM; v. 20, n. 1, p. 10-pg., 2020-09-29.
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 (T-4) 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 T-4(SCH + T-4). 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, T(4)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. (AU)

FAPESP's process: 17/23169-1 - Thyroid hormones action on 3xTg-AD (APPswe, PS1m146v, tauP301L) Alzheimer's Disease mice model
Grantee:Gisele Giannocco
Support Opportunities: Regular Research Grants
FAPESP's process: 18/22763-0 - Ancient DNA, bioengineering and brain "organoids": study of thyroid hormone homeostasis and Alzheimer's Disease markers in NOVA1 gene CRISPR edited stem cells
Grantee:Janaína Sena de Souza
Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
FAPESP's process: 17/07053-3 - Effect of thyroid hormone on the brain of 3xTg-AD mice, model of Alzheimer's Disease, on glucose and cholesterol metabolism
Grantee:Janaína Sena de Souza
Support Opportunities: Scholarships in Brazil - Post-Doctoral