Propylthiouracil Increases Sodium/Iodide Symporter Gene Expression and Iodide Uptake in Rat Thyroid Cells in the Absence of TSH

Abstract

Background: Propylthiouracil (PTU) and methimazole (MMI) are drugs that are widely used to treat Graves' disease. Although both exert an antithyroid effect primarily by blocking thyroid peroxidase activity, their molecular structure and other actions are different. We hypothesized that PTU and MMI may have differential effects on thyroid-specific gene expression and function. Methods: The effects of PTU and MMI on thyroid-specific gene expression and function were examined in rat thyroid FRTL-5 cells using DNA microarray, reverse transcriptase (RT)-polymerase chain reaction (PCR), real-time PCR, Western blot, immunohistochemistry, and radioiodine uptake studies. Results: DNA microarray analysis showed a marked increase in sodium/iodide symporter (NIS) gene expression after PTU treatment, whereas MMI had no effect. RT-PCR and real-time PCR analysis revealed that PTUinduced NIS mRNA levels were comparable to those elicited by thyroid-stimulating hormone (TSH). PTU increased 5¢-1880-bp and 5¢-1052-bp activity of the rat NIS promoter. While PTU treatment also increased NIS protein levels, the size of the induced protein was smaller than that induced by TSH, and the protein localized predominantly in the cytoplasm rather than the plasma membrane. Accumulation of 125 I in FRTL-5 cells was increased by PTU stimulation, but this effect was weaker than that produced by TSH. Conclusions: We found that PTU induces NIS expression and iodide uptake in rat thyroid FRTL-5 cells in the absence of TSH. Although PTU and MMI share similar antithyroid activity, their effects on other thyroid functions appear to be quite different, which could affect their therapeutic effectiveness.

Effect of Soybean, Virgin Coconut and Moringa oleifera Seed Oils on the Propylthiouracil Induced Hypothyroidism in Rats

“…Fumarola et al (2010) stated that PTU inhibits iodine oxidation and monodotyrosine ionization. It is also prevented the coupling stage and inhibited the peripheral conversion of (T4) to (T3).So, it suppresses the synthesis of thyroid hormones by blocking the activity of thyroid peroxidase (Sue et al, 2012).…”

Acute Effects of Potassium Iodide after Propylthiouracil Administration: Contents of Iodine and Selenium in the Thyroid, Pituitary, Adrenal Glands and Ovaries of Female Rats

“…As described before [10], the absorption of 131I absorption by the thyroid gland increases during the rebound effect and is probably connected to the NIS expression increase after administration of KI [2] and PTU [15]. This phenomenon is a reaction to the thyroid gland blockade and the change of iodine content in the thyroid gland.…”

“…In general, it is considered that the thyroid gland saturates with iodine within one week and then saturation blocks further absorption of iodine. M. Sue confirmed this premise [15], by determining that PTU causes the expression of the sodium iodide symporter (NIS) to increase in thyrocytes in absence of the thyroid-stimulating hormone (TSH). In a previous study using EPMA under iodineinduced thyroid blockade, we found that the expression of NIS in the thyroid gland increased during the first 5 days of the blockade, along with a decrease of intrathyroidal iodine [2].…”

Methimazole Inhibits the Expression of GFAP and the Migration of Astrocyte in Scratched Wound Model In Vitro

“…And we found there were no obvious toxic effects of methimazole on the astrocytes (Figure 1(a)). Thereafter, 5 mM was used for the following study in the scratch wound model based on the cell viability result and a previous report on a cell culture model [19]. Next, we tested our primary hypothesis whether methimazole could inhibit the upregulation of the GFAP protein in a scratched astrocyte culture.…”

“…Methimazole was purchased from Sigma and dissolved in DMEM. The doses used in the study were referred from the previous publication [19]. Animal protocols were approved by the Experimental Animal Ethics Committee of China-Japan Union Hospital, Jilin University, Jilin Province, China.…”