Thyroxine replacement modifies changes in deiodinase and thyroid hormone transporter expression induced by subclinical h
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ORIGINAL ARTICLE
Thyroxine replacement modifies changes in deiodinase and thyroid hormone transporter expression induced by subclinical hypothyroidism in rats Kelen Carneiro Oliveira 1 & Roberto Laureano-Melo 2 & Rodrigo Rodrigues da Conceição 1 & Janaina Sena de Souza 1 & Wellington da Silva Cortês 2 & Mônica Akemi Sato 3 & Maria Izabel Chiamolera 1 & Rui Monteiro Maciel 1 & Gisele Giannocco 1,4 Received: 26 February 2020 / Accepted: 17 September 2020 # Hellenic Endocrine Society 2020
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. Keywords Subclinical hypothyroidism . Thyroxine replacement . Deiodinases . Thyroid hormone transporters . Crym
Kelen Carneiro Oliveira, Roberto Laureano-Melo and Rodrigo Rodrigues da Conceição contributed equally to this work. * Rodrigo Rodrigues da Conceição [email protected]
2
Programa Multicêntrico de Pós-Graduação em Ciências Fisiológicas, Instituto de Ciências Biológicas e da Saúde, Universidade Federal Rural do Rio de Janeiro Brazil; Federal Rural University of Rio de Janeiro, BR 465, Km 7, PQ Room 01, Seropedica, Rio de Janeiro 23897-000, Brazil
3
Departamento de Morfologia e Fisiologia, Faculdade de Medicina do ABC, Av. Lauro Gomes, 2000 - Vila Sacadura Cabral, Santo André, SP 09060-870, Brazil
4
Departamento de Ciências Biológicas, Universidade Federal
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