Administration of 3,5-diiodothyronine (3,5-T2) causes central hypothyroidism and stimulates thyroid-sensitive tissues

Alvaro Souto Padron, Ruy Andrade Louzada Neto, Thiago Urgal Pantaleão, Maria Carolina De Souza Dos Santos, Renata Lopes Araujo, Bruno Moulin De Andrade, Monique Da Silva Leandro, João Pedro Saar Werneck De Castro, Andrea Claudia Freitas Ferreira, Denise Pires De Carvalho

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

In general, 3,5-diiodothyronine (3,5-T2) increases the resting metabolic rate and oxygen consumption, exerting short-term beneficial metabolic effects on rats subjected to a high-fat diet. Our aim was to evaluate the effects of chronic 3,5-T2 administration on the hypothalamus-pituitary-thyroid axis, body mass gain, adipose tissue mass, and body oxygen consumption in Wistar rats from 3 to 6 months of age. The rats were treated daily with 3,5-T2 (25, 50, or 75 μg/100 g body weight, s.c.) for 90 days between the ages of 3 and 6 months. The administration of 3,5-T2 suppressed thyroid function, reducing not only thyroid iodide uptake but also thyroperoxidase, NADPH oxidase 4 (NOX4), and thyroid type 1 iodothyronine deiodinase (D1 (DIO1)) activities and expression levels, whereas the expression of the TSH receptor and dual oxidase (DUOX) were increased. Serum TSH, 3,30,5-triiodothyronine, and thyroxine were reduced in a 3,5-T2 dose-dependent manner, whereas oxygen consumption increased in these animals, indicating the direct action of 3,5-T2 on this physiological variable. Type 2 deiodinase activity increased in both the hypothalamus and the pituitary, and D1 activities in the liver and kidney were also increased in groups treated with 3,5-T2. Moreover, after 3 months of 3,5-T2 administration, body mass and retroperitoneal fat pad mass were significantly reduced, whereas the heart rate and mass were unchanged. Thus, 3,5-T2 acts as a direct stimulator of energy expenditure and reduces body mass gain; however, TSH suppression may develop secondary to 3,5-T2 administration.

Original languageEnglish (US)
Pages (from-to)415-427
Number of pages13
JournalJournal of Endocrinology
Volume221
Issue number3
DOIs
StatePublished - Jun 2014
Externally publishedYes

Keywords

  • 3,5-T2
  • Deiodinase
  • Thyroid hormone metabolism
  • TSH

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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