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

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, 3,3',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.

• Authors: 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
• Journal: The Journal of endocrinology (J Endocrinol) Vol. 221 Issue 3 Pg. 415-27 (Jun 2014) ISSN: 1479-6805 [Electronic] England
• PMID: 24692290 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 The authors.

Chemical References

• Diiodothyronines
• Flavoproteins
• Iodides
• Receptors, Thyrotropin
• Triiodothyronine
• 3,5-diiodothyronine
• Thyrotropin
• Dual Oxidases
• iodothyronine deiodinase type I
• iodothyronine deiodinase type II
• Iodide Peroxidase
• NADPH Oxidase 4
• NADPH Oxidases
• Nox4 protein, rat
• Duox1 protein, rat
• Duox2 protein, rat
• Thyroxine

Topics

• Animals
• Basal Metabolism (drug effects)
• Diiodothyronines (administration & dosage, pharmacology)
• Dual Oxidases
• Flavoproteins (genetics, metabolism)
• Hypothalamo-Hypophyseal System (drug effects, metabolism, physiopathology)
• Hypothyroidism (blood, genetics, metabolism)
• Immunoblotting
• Iodide Peroxidase (metabolism)
• Iodides (metabolism)
• Kidney (drug effects, metabolism)
• Liver (drug effects, metabolism)
• Male
• NADPH Oxidase 4
• NADPH Oxidases (genetics, metabolism)
• Oxygen Consumption (drug effects)
• Rats
• Rats, Wistar
• Receptors, Thyrotropin (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Thyroid Gland (drug effects, metabolism, physiopathology)
• Thyrotropin (blood)
• Thyroxine (blood)
• Triiodothyronine (blood)