Home | Orthoiodosupplementation | Body | Disease | Special | Overviews

Thyroid Physiology

Thyroid Disease

Cancer

Thyroid Cancer

• Abraham

• Carrasco

• Chow

• Feldt-Rasmussen

• Filetti, Arturi

• Franceschi

• Gartner

• Jeong, Kim

• Kogai

• Kristensen

• Maier, Krohn, Paschke

• Mastorakos

• Mutaku, Many

• Neumann, Paschke

• Park

• Ringel

• Schlumberger

• Skubis-Zegadlo

• Smit

• Son

• Spitzweg

• Venkataraman

• Verkooijen

• West

• Xing, Sidransky

• Zaichick

Neumann, Paschke

Lack of correlation for sodium iodide symporter mRNA and protein expression and analysis of sodium iodide symporter promoter methylation in benign cold thyroid nodules.

Neumann S, Schuchardt K, Reske A, Reske A, Emmrich P, Paschke R.

Thyroid. 2004 Feb;14(2):99-111.

"Cold thyroid nodules (CTNs) are characterized by a reduced iodide uptake in comparison to normal thyroid tissue. The sodium iodide symporter (NIS) is the first step in thyroid hormone synthesis and mediates the active iodide transport in the thyroid cells suggesting that decreased iodide uptake could be a result of changes in NIS expression or molecular defects in the NIS gene. In contrast to previous studies, an intraindividual comparison of NIS mRNA expression in CTNs and their corresponding surrounding tissue was performed using direct detection of NIS mRNA. A significant reduction in NIS mRNA expression was detected in 86% of the 14 investigated CTNs. We hypothesized that human sodium iodide symporter (hNIS) transcriptional failure could be caused by primary molecular NIS gene defects and/or methylation of DNA in the NIS promoter. However, no mutation in the NIS cDNA nor in the NIS promoter region upstream up to-443 bp from the ATG start codon was detected. Therefore, primary molecular NIS gene defects were excluded. However, in 50% of CTNs with reduced NIS mRNA expression, the promoter region was hypermethylated. NIS mRNA expression in these hypermethylated CTNs only reached a maximum of 30% of the corresponding surrounding tissue. Hence, methylation of CpG islands in the NIS promotor could be a regulatory mechanism of NIS transcription in CTNs. Immunoblot revealed absent hNIS protein expression in the total cell membrane fraction in 45% of investigated nodules. In the majority of the remaining CTNs NIS protein expression was decreased in the nodule tissue compared to the corresponding surrounding tissue. For investigating protein expression immunhistochemistry has two advantages. First, the whole nodule area can be investigated, and second, NIS expression can be detected in areas where an immunoblot of a cell membrane fraction is negative. Interestingly, immunhistochemistry revealed higher NIS expression in 50% of CTNs compared to their corresponding surrounding tissues and NIS staining was predominantly intracellular. These data demonstrate that NIS protein expression does not reflect NIS mRNA expression. Therefore, factors that affect targeting of NIS to the plasma membrane are likely to be affected."
 

Sodium/iodide symporter mRNA expression in cold thyroid nodules.

Paschke R, Neumann S.

Exp Clin Endocrinol Diabetes. 2001;109(1):45-6. Review.

[abstract only]

"Clinical and experimental data suggest a low thyroid hormone synthesis in cold thyroid nodules (CTN). Therefore, the Na(+)/I(-)-symporter (NIS) as the first step in the thyroid hormone synthesis could be a possible candidate gene in the pathogenesis of CTNs. A reduction of NIS transcripts in CTNs compared to samples of normal thyroid tissues with large inter-individual variations ranging from 2- to 700-fold reductions was observed with real-time RT-PCR. Therefore, the aim of our investigations was to perform an intra-individual comparison of NIS expression in CTNs. Moreover, we used direct detection of NIS mRNA by RNase protection assay (RPA). We investigated 14 patients with one CTN for NIS mRNA expression. NIS mRNA transcripts from nodule and surrounding tissue were examined by RPA. A significantly reduced NIS expression was detected in 86% of the CTNs compared to their corresponding surrounding tissue. The level of NIS expression was decreased to more than 65% in 10 CTNs (72% of the nodules). Two of the 14 nodules showed a decrease of NIS mRNA expression of 42%, and 32%, while no significant differences could be detected in 2 cold nodules. Compared to other studies the intra-individual comparison of NIS mRNA expression revealed a much lower variation of reduced NIS expression in CTNs. Further studies should try to identify molecular factors like post-transcriptional modifications or alterations in iodide organification which are likely to be involved in the pathogenesis of CTNs."
 

 Home | Orthoiodosupplementation | Body | Disease | Special Topics | Overviews  

The Iodine Group | Books | Disclaimers | Contact Us | Search  

  Copyright: Zoe, 2006.