MCT8 is Downregulated by Short Time Iodine Overload in the Thyroid Gland of Rats

Abstract

Wolff-Chaikoff effect is characterized by the blockade of thyroid hormone synthesis and secretion due to iodine overload. However, the regulation of monocarboxylate transporter 8 during Wolff-Chaikoff effect and its possible role in the rapid reduction of T4 secretion by the thyroid gland remains unclear. Patients with monocarboxylate transporter 8 gene loss-of-function mutations and monocarboxylate transporter 8 knockout mice were shown to have decreased serum T4 levels, indicating that monocarboxylate transporter 8 could be involved in the secretion of thyroid hormones from the thyroid gland. Herein, we aimed to evaluate the regulation of monocarboxylate transporter 8 during the Wolff-Chaikoff effect and the escape from iodine overload, besides the importance of iodine organification for this regulation. Monocarboxylate transporter 8 mRNA and protein levels significantly decreased after 1 day of NaI administration to rats, together with decreased serum T4; while no alteration was observed in LAT2 expression. Moreover, both monocarboxylate transporter 8 expression and serum T4 was restored after 6 days of NaI. The inhibition of thyroperoxidase activity by methimazole prevented the inhibitory effect of NaI on thyroid monocarboxylate transporter 8 expression, suggesting that an active thyroperoxidase is necessary for MCT8 downregulation by iodine overload, similarly to other thyroid markers, such as sodium iodide symporter. Therefore, we conclude that thyroid monocarboxylate transporter 8 expression is downregulated during iodine overload and that the normalization of its expression parallels the escape phenomenon. These data suggest a possible role for monocarboxylate transporter 8 in the changes of thyroid hormones secretion during the Wolff-Chaikoff effect and escape.

New insights into thyroid hormone action

“…Transporters may also play a role in determining circulating levels of thyroid hormones. Indeed, MCT8 is expressed on the basolateral membrane of thyrocytes and appears to be necessary for T4 efflux from the gland (de Souza et al, 2015) (Trajkovic-Arsic et al, 2010). Furthermore, two SNPs in MCT8 have been associated with differences in circulating T3: the first SNP causes a missense mutation in serine107 to proline; the second is intronic and the effect on transporter expression is not yet understood (G.…”

“…At the protein level, long-term iodine deficiency increased the localization of MCT8 to the membrane of thyrocytes, and this effect was prevented by treatment with T3 (Hu et al, 2014). In contrast, short term iodine overload down-regulated MCT8 mRNA but not LAT2 in the thyroid gland (de Souza et al, 2015). …”

Toxicology of Repeated Iodine Thyroid Blocking in Adult Rat

“…NIS, PDS, TPO, DUOX, Tg, MCT8…) [29,30], circulating TH levels is tightly regulated under physiological circumstances and exert a major impact on the body homeostasis. Acute excess of iodine could lead to a transient downregulation of thyroid hormones level, the so-called Wolff-Chaikoff effect, this down-regulation leads to the up-regulation of TSH, thereby affecting gene expression in the thyroid [19,22,31,32].…”

“…Wolff and Chaikoff demonstrated in 1948 that an excess of iodide in rats may transiently disrupt thyroid function, the well-known Wolff-Chaikoff effect is characterized by a decrease in and delayed iodide organification [18]. This affects many steps of thyroid hormone synthesis and secretion; such iodide entrance and organification, iodide efflux through the colloid, intra-thyroidal iodide pool regeneration, and thyroid hormones transport [19][20][21][22]. This effect could lead to a temporary variation in thyroid hormones level, which exerts a major impact on development, growth, and metabolism [19,22].…”

“…This affects many steps of thyroid hormone synthesis and secretion; such iodide entrance and organification, iodide efflux through the colloid, intra-thyroidal iodide pool regeneration, and thyroid hormones transport [19][20][21][22]. This effect could lead to a temporary variation in thyroid hormones level, which exerts a major impact on development, growth, and metabolism [19,22]. Normally after a few days, thyroid hormone levels return to normal the so-called escape phenomenon.…”