scholarly journals Molecular Analysis of the Sodium/Iodide Symporter: Impact on Thyroid and Extrathyroid Pathophysiology

2000 ◽  
Vol 80 (3) ◽  
pp. 1083-1105 ◽  
Author(s):  
Antonio De la Vieja ◽  
Orsolya Dohan ◽  
Orlie Levy ◽  
Nancy Carrasco
Keyword(s):  
Thyroid Cancer ◽  
Molecular Analysis ◽  
Posttranslational Modifications ◽  
Wide Spectrum ◽  
Sodium Iodide Symporter ◽  
Iodide Transport ◽  
Thyroid Hormone Biosynthesis ◽  
Lactating Mammary Gland ◽  
Transport Defect ◽  
Radioiodide Therapy

The Na+/I−symporter (NIS) is an intrinsic membrane protein that mediates the active transport of iodide into the thyroid and other tissues, such as salivary glands, gastric mucosa, and lactating mammary gland. NIS plays key roles in thyroid pathophysiology as the route by which iodide reaches the gland for thyroid hormone biosynthesis and as a means for diagnostic scintigraphic imaging and for radioiodide therapy in hyperthyroidism and thyroid cancer. The molecular characterization of NIS started with the 1996 isolation of a cDNA encoding rat NIS and has since continued at a rapid pace. Anti-NIS antibodies have been prepared and used to study NIS topology and its secondary structure. The biogenesis and posttranslational modifications of NIS have been examined, a thorough electrophysiological analysis of NIS has been conducted, the cDNA encoding human NIS (hNIS) has been isolated, the genomic organization of hNIS has been elucidated, the regulation of NIS by thyrotropin and I− has been analyzed, the regulation of NIS transcription has been studied, spontaneous NIS mutations have been identified as causes of congenital iodide transport defect resulting in hypothyroidism, the roles of NIS in thyroid cancer and thyroid autoimmune disease have been examined, and the expression and regulation of NIS in extrathyroidal tissues have been investigated. In gene therapy experiments, the rat NIS gene has been transduced into various types of human cells, which then exhibited active iodide transport and became susceptible to destruction with radioiodide. The continued molecular analysis of NIS clearly holds the potential of an even greater impact on a wide spectrum of fields, ranging from structure/function of transport proteins to the diagnosis and treatment of cancer, both in the thyroid and beyond.

The Sodium/Iodide Symporter (NIS): Characterization, Regulation, and Medical Significance

2003 ◽  
Vol 24 (1) ◽  
pp. 48-77 ◽  
Author(s):  
Orsolya Dohán ◽  
Antonio De la Vieja ◽  
Viktoriya Paroder ◽  
Claudia Riedel ◽  
Mona Artani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Thyroid Cancer ◽  
Thyroid Hormone ◽  
Posttranslational Modifications ◽  
Posttranscriptional Regulation ◽  
Basolateral Membrane ◽  
Breast Cancer Diagnosis ◽  
Sodium Iodide Symporter ◽  
Thyroid Hormone Biosynthesis ◽  
Hormone Biosynthesis

Abstract The Na+/I− symporter (NIS) is an integral plasma membrane glycoprotein that mediates active I− transport into the thyroid follicular cells, the first step in thyroid hormone biosynthesis. NIS-mediated thyroidal I− transport from the bloodstream to the colloid is a vectorial process made possible by the selective targeting of NIS to the basolateral membrane. NIS also mediates active I− transport in other tissues, including salivary glands, gastric mucosa, and lactating mammary gland, in which it translocates I− into the milk for thyroid hormone biosynthesis by the nursing newborn. NIS provides the basis for the effective diagnostic and therapeutic management of thyroid cancer and its metastases with radioiodide. NIS research has proceeded at an astounding pace after the 1996 isolation of the rat NIS cDNA, comprising the elucidation of NIS secondary structure and topology, biogenesis and posttranslational modifications, transcriptional and posttranscriptional regulation, electrophysiological analysis, isolation of the human NIS cDNA, and determination of the human NIS genomic organization. Clinically related topics include the analysis of congenital I− transport defect-causing NIS mutations and the role of NIS in thyroid cancer. NIS has been transduced into various kinds of cancer cells to render them susceptible to destruction with radioiodide. Most dramatically, the discovery of endogenous NIS expression in more than 80% of human breast cancer samples has raised the possibility that radioiodide may be a valuable novel tool in breast cancer diagnosis and treatment.

scholarly journals The importance of sodium/iodide symporter (NIS) for thyroid cancer management

2007 ◽  
Vol 51 (5) ◽  
pp. 672-682 ◽  
Author(s):  
Denise P. Carvalho ◽  
Andrea C.F. Ferreira
Keyword(s):  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Therapeutic Tool ◽  
Iodide Transport ◽  
Cancer Management ◽  
Thyroid Hormone Biosynthesis ◽  
Nis Gene ◽  
Hormone Biosynthesis ◽  
Tumoral Cells

The thyroid gland has the ability to uptake and concentrate iodide, which is a fundamental step in thyroid hormone biosynthesis. Radioiodine has been used as a diagnostic and therapeutic tool for several years. However, the studies related to the mechanisms of iodide transport were only possible after the cloning of the gene that encodes the sodium/iodide symporter (NIS). The studies about the regulation of NIS expression and the possibility of gene therapy with the aim of transferring NIS gene to cells that normally do not express the symporter have also become possible. In the majority of hypofunctioning thyroid nodules, both benign and malignant, NIS gene expression is maintained, but NIS protein is retained in the intracellular compartment. The expression of NIS in non-thyroid tumoral cells in vivo has been possible through the transfer of NIS gene under the control of tissue-specific promoters. Apart from its therapeutic use, NIS has also been used for the localization of metastases by scintigraphy or PET-scan with 124I. In conclusion, NIS gene cloning led to an important development in the field of thyroid pathophysiology, and has also been fundamental to extend the use of radioiodine for the management of non-thyroid tumors.

scholarly journals Thyroglobulin in smoking mothers and their newborns at delivery suggests autoregulation of placental iodide transport overcoming thiocyanate inhibition

2013 ◽  
Vol 168 (5) ◽  
pp. 723-731 ◽  
Author(s):  
Stine L Andersen ◽  
Susanne B Nøhr ◽  
Chun S Wu ◽  
Jørn Olsen ◽  
Klaus M Pedersen ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Iodine Deficiency ◽  
Maternal Smoking ◽  
Maternal Serum ◽  
Sodium Iodide Symporter ◽  
Hormone Production ◽  
Cord Serum ◽  
Iodide Transport ◽  
Lactating Mammary Gland ◽  
The Impact

BackgroundPlacental transport of iodide is required for fetal thyroid hormone production. The sodium iodide symporter (NIS) mediates active iodide transport into the thyroid and the lactating mammary gland and is also present in placenta. NIS is competitively inhibited by thiocyanate from maternal smoking, but compensatory autoregulation of iodide transport differs between organs. The extent of autoregulation of placental iodide transport remains to be clarified.ObjectiveTo compare the impact of maternal smoking on thyroglobulin (Tg) levels in maternal serum at delivery and in cord serum as markers of maternal and fetal iodine deficiency.MethodsOne hundred and forty healthy, pregnant women admitted for delivery and their newborns were studied before the iodine fortification of salt in Denmark. Cotinine in urine and serum classified mothers as smokers (n=50) or nonsmokers (n=90). The pregnant women reported on intake of iodine-containing supplements during pregnancy and Tg in maternal serum at delivery and in cord serum were analyzed.ResultsIn a context of mild-to-moderate iodine deficiency, smoking mothers had significantly higher serum Tg than nonsmoking mothers (mean Tg smokers 40.2 vs nonsmokers 24.4 μg/l, P=0.004) and so had their respective newborns (cord Tg 80.2 vs 52.4 μg/l, P=0.006), but the ratio between Tg in cord serum and maternal serum was not significantly different in smokers compared with nonsmokers (smoking 2.06 vs nonsmoking 2.22, P=0.69).ConclusionMaternal smoking increased the degree of iodine deficiency in parallel in the mother and the fetus, as reflected by increased Tg levels. However, placental iodide transport seemed unaffected despite high thiocyanate levels, suggesting that thiocyanate-insensitive iodide transporters alternative to NIS are active or that NIS in the placenta is autoregulated to keep iodide transport unaltered.

scholarly journals Cloning of the mouse sodium iodide symporter and its expression in the mammary gland and other tissues

2001 ◽  
Vol 170 (1) ◽  
pp. 185-196 ◽  
Author(s):  
B Perron ◽  
AM Rodriguez ◽  
G Leblanc ◽  
T Pourcher
Keyword(s):  
Mammary Gland ◽  
Mammalian Cells ◽  
Sodium Iodide ◽  
Distribution Analysis ◽  
Sodium Iodide Symporter ◽  
Iodide Uptake ◽  
Reading Frame ◽  
Hormone Synthesis ◽  
Iodide Transport ◽  
Lactating Mammary Gland

Iodide concentration in milk by mammals is a necessary step for thyroid hormone synthesis by the newborn. With the purpose of using the mouse as an animal model to analyse the role of the sodium iodide symporter (NIS) in iodide transport and its regulation in the mammary gland, mouse NIS (mNIS) cDNA was isolated from lactating mice. The cloned sequence shows an open reading frame of 1854 nucleotides encoding a protein of 618 amino acids highly homologous to the rat and human NIS (95% and 81% identity respectively). Expression of mNIS in cultured mammalian cells induced cellular iodide accumulation. This iodide uptake process is sodium dependent and inhibited by thiocyanate and perchlorate. Tissue distribution analysis revealed that mNIS mRNAs are predominantly expressed in thyroid, stomach and in the lactating mammary gland and are present to a lower extent in several other tissues. Our data show for the first time that the level of mNIS mRNA is upregulated in the mammary gland during lactation.

scholarly journals Congenital Hypothyroidism Caused by a PAX8 Gene Mutation Manifested as Sodium/Iodide Symporter Gene Defect

2010 ◽  
Vol 2010 ◽  
pp. 1-3 ◽  
Author(s):  
Wakako Jo ◽  
Katsura Ishizu ◽  
Kenji Fujieda ◽  
Toshihiro Tajima
Keyword(s):  
Thyroid Gland ◽  
Congenital Hypothyroidism ◽  
Sodium Iodide ◽  
Present Report ◽  
Sodium Iodide Symporter ◽  
Loss Of Function ◽  
Laboratory Findings ◽  
Iodide Transport ◽  
Transport Defect ◽  
Pax8 Gene

Loss-of-function mutations of the PAX8 gene are considered to mainly cause congenital hypothyroidism (CH) due to thyroid hypoplasia. However, some patients with PAX8 mutation have demonstrated a normal-sized thyroid gland. Here we report a CH patient caused by a PAX8 mutation, which manifested as iodide transport defect (ITD). Hypothyroidism was detected by neonatal screening and L-thyroxine replacement was started immediately. Although I scintigraphy at 5 years of age showed that the thyroid gland was in the normal position and of small size, his iodide trapping was low. The ratio of the saliva/plasma radioactive iodide was low. He did not have goiter; however laboratory findings suggested that he had partial ITD. Gene analyses showed that the sodium/iodide symporter (NIS) gene was normal; instead, a mutation in the PAX8 gene causing R31H substitution was identified. The present report demonstrates that individuals with defective PAX8 can have partial ITD, and thus genetic analysis is useful for differential diagnosis.

A Novel V59E Missense Mutation in the Sodium Iodide Symporter Gene in a Family with Iodide Transport Defect

Thyroid ◽  
2000 ◽  
Vol 10 (6) ◽  
pp. 471-474 ◽  
Author(s):  
Hirokazu Fujiwara ◽  
Ke-ita Tatsumi ◽  
Susumu Tanaka ◽  
Masahiro Kimura ◽  
Osamu Nose ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Iodide Transport ◽  
Transport Defect
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