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.

Transport of iodide into thyrocytes, a fundamental step in thyroid hormone biosynthesis, depends on the presence of the sodium-iodide symporter (NIS). The importance of the NIS for diagnosis and treatment of diseases has raised several questions about its physiological control. The goal of this study was to evaluate the influence of thyroid iodine content on NIS regulation by thyrotrophin (TSH) in vivo. We showed that 15-min thyroid radioiodine uptake can be a reliable measurement of NIS activity in vivo. The effect of TSH on the NIS was evaluated in rats treated with 1-methyl-2-mercaptoimidazole (MMI; hypothyroid with high serum TSH concentrations) for 21 days, and after 1 (R1d), 2 (R2d), or 5 (R5d) days of withdrawal of MMI. NIS activity was significantly greater in both MMI and R1d rats. In R2d and R5d groups, thyroid iodide uptake returned to normal values, despite continuing high serum TSH, possibly as a result of the re-establishment of iodine organification after withdrawal of MMI. Excess iodine (0·05% NaI for 6 days) promoted a significant reduction in thyroid radioiodide uptake, an effect that was blocked by concomitant administration of MMI, confirming previous findings that iodine organification is essential for the iodide transport blockade seen during iodine overload. Therefore, our data show that modulation of the thyroid NIS by TSH depends primarily on thyroid iodine content and, further, that the regulation of NIS activity is rapid.

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Thyroid diseases, such as autoimmune disease and benign and malignant nodules, are more prevalent in women than in men, but the mechanisms involved in this sex difference is still poorly defined. H 2 O 2 is produced at high levels in the thyroid gland and regulates parameters such as cell proliferation, migration, survival, and death; an imbalance in the cellular oxidant-antioxidant system in the thyroid may contribute to the greater incidence of thyroid disease among women. Recently, we demonstrated the existence of a sexual dimorphism in the thyrocyte redox balance, characterized by higher H 2 O 2 production, due to higher NOX4 and Poldip2 expression, and weakened enzymatic antioxidant defense in the thyroid of adult female rats compared with male rats. In addition, 17b-estradiol administration increased NOX4 mRNA expression and H 2 O 2 production in thyroid PCCL3 cells. In this review, we discuss the possible involvement of oxidative stress in estrogenrelated thyroid pathophysiology. Our current hypothesis suggests that a redox imbalance elicited by estrogen could be involved in the sex differences found in the prevalence of thyroid dysfunctions.

Melatonin has been shown to regulate several immune functions, and some authors showed that leukocytes are also able to produce the indolamine. In fact, it seems to take part in some immunoregulatory axis, including that related to interferon (IFN) production. So, we evaluated the rate of tryptophan consumption and melatonin and serotonin production in peritoneal cavity-isolated macrophages and the effect of IFN-alpha and -gamma, lipopolysaccharide (LPS), and phorbol myristate acetate (PMA) on such parameters. Our results indicate that macrophages obtained from the peritoneal cavity of normal rats when incubated with tryptophan show an increase in arylalkylamine N-acetyltransferase activity that corresponds to an increased melatonin production, as determined in the incubation medium. This process is regulated by IFN-alpha and -gamma, PMA, LPS, and the serum from tumor-bearing rats, opening the possibility of speculation about different immunoregulatory loops acting through the balance of melatonin/serotonin production by such cells.