Deiodinase Activities in Thyroids and Tissues of Iodine-Deficient Female Rats

Abstract

Severe iodine deficiency is characterized by goiter, preferential synthesis, and secretion of T(3) in thyroids, hypothyroxinemia in plasma and tissues, normal or low plasma T(3), and slightly increased plasma TSH. We studied changes in deiodinase activities and mRNA in several tissues of rats maintained on low-iodine diets (LIDs) or LIDs supplemented with iodine (LID+I). T(4) and T(3) concentrations decreased in plasma, tissues, and thyroids of LID rats, and T(4) decreased more than T(3) (50%). The highest type 1 iodothyronine deiodinase (D1) activities were found in the thyroid, kidney, and the liver; pituitary, lung, and ovary had lower D1 activities; but the lowest levels were found in the heart and skeletal muscle. D1 activity decreased in all tissues of LID rats (10-40% of LID+I rats), except for ovary and thyroids, which D1 activity increased 2.5-fold. Maximal type 2 iodothyronine deiodinase (D2) activities were found in thyroid, brown adipose tissue, and pituitary, increasing 6.5-fold in thyroids of LID rats and about 20-fold in the whole gland. D2 always increased in response to LID, and maximal increases were found in the cerebral cortex (19-fold), thyroid, brown adipose tissue, and pituitary (6-fold). Lower D2 activities were found in the ovary, heart, and adrenal gland, which increased in LID. Type 3 iodothyronine deiodinase activity was undetectable. Thyroidal Dio1 and Dio2 mRNA increased in the LID rats, and Dio1 decreased in the lung, with no changes in mRNA expression in other tissues. Our data indicate that LID induces changes in deiodinase activities, especially in the thyroid, to counteract the low T(4) synthesis and secretion, contributing to maintain the local T(3) concentrations in the tissues with D2 activity.

The effects of caloric restriction and age on thyroid hormone signalling in the heart of rats

“…Type 2 deiodinase expression in rodent heart is much lower than in human heart (Croteau et at., 1996), therefore rodents are not considered a suitable model for human D2 regulation. Cardiac D2 mRNA and activity in mouse and rats has, however, been demonstrated to respond to changes in thyroid hormone levels induced by hypothyroidism provoked by methimazol treatment (Wagner et al, 2003) or iodine deficiency (Lavado-Autric et al, 2013) and attenuated by T3 administration (Wagner et al, 2003). This could indicate that in our study, local changes in thyroid hormone evoked by CR were not sufficient to alter D2 expression.…”

American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models

“…The main consequences of iodine deficiency are goiter, hypothyroxinemia (242), increased NIS expression (331), increased monoiodotyrosine (MIT)/diiodotyrosine (DIT) and T 3 /T 4 ratios within the thyroglobulin (332,333), preferential T 3 synthesis and secretion by the thyroid (242,332), increased D1 and D2 activities in the thyroid and D2 activity in BAT (334,335), low T 4 in plasma and tissues (71,336,337), and a TSH concentration that is slightly elevated, together with a normal or slightly decreased T 3 level in serum and several tissues (71). Tissue uptake of T 4 and T 3 increases.…”

Thyroid hormones and deiodinase activities in plasma and tissues from East Greenland polar bears (Ursus maritimus) during winter season

“…However, circulating levels of THs are thought not to reflect intracellular TH status and do therefore not give information about TH status in tissues (Bianco 2013;Dentice et al 2013). Levels of THs and deiodinase activities in various tissues have been reported in studies using experimental animals (McCann et al 1984;Morreale de Escobar et al 1985;van Doorn et al 1985;Raasmaja et al 1996;Viluksela et al 2004;Kunisue et al 2011;Lavado-Autric et al 2013), but there are to our knowledge no reports of levels of THs or deiodinase activities in tissues of free-ranging polar bears or other arctic wildlife species.…”

“…Analysis of thyroid hormones and deiodinase activity in liver, kidney and muscle I]-rT3) used in the analyses were synthesised at the laboratory using chloramine-T and T3, 3,5-T2 and 3 0 ,3-T2 as substrates, respectively, as described by Weeke and Orskov (1973 Thyroid hormone concentrations in liver, muscle and kidney Total T4 and T3 in liver (T4 L , T3 L ), kidney (T4 K , T3 K ) and muscle (T4 M , T3 M ) samples were analysed by RIAs after extraction and purification of the tissue samples, as originally described in Morreale de Escobar et al (1985) and later in Lavado-Autric et al (2013). In short, frozen tissue samples were homogenised in methanol, and tracer amounts of [ 131 I]-T4 and [ 125 I]-T3 were added to each sample.…”

“…The analyses of D1 and D2 activities were performed as described in Lavado-Autric et al (2013). Tissue homogenates were prepared in a buffer [1:30 wt/vol] consisting of 0.32 M sucrose, 10 mm HEPES buffer and dithiothreitol (DTT; 1 mM for D1 and 10 mM for D2), pH 7.0.…”