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 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.

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.

The Impact of Iodine Excess on Thyroid Hormone Biosynthesis and Metabolism in Rats

2009 ◽  
Vol 130 (1) ◽  
pp. 72-85 ◽  
Author(s):  
K. Wang ◽  
Y. N. Sun ◽  
J. Y. Liu ◽  
L. Zhang ◽  
Y. Ye ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Iodine Excess ◽  
Thyroid Hormone Biosynthesis ◽  
Hormone Biosynthesis ◽  
The Impact

scholarly journals The Sodium-Iodide Symporter NIS and Pendrin in Iodide Homeostasis of the Thyroid

Endocrinology ◽  
2009 ◽  
Vol 150 (3) ◽  
pp. 1084-1090 ◽  
Author(s):  
Aigerim Bizhanova ◽  
Peter Kopp
Keyword(s):  
Autosomal Recessive ◽  
Sodium Iodide ◽  
Basolateral Membrane ◽  
Sensorineural Deafness ◽  
Sodium Iodide Symporter ◽  
Pendred Syndrome ◽  
Iodide Uptake ◽  
Anion Transporter ◽  
Thyroid Hormone Biosynthesis ◽  
Biallelic Mutations

Thyroid hormones are essential for normal development and metabolism. Thyroid hormone biosynthesis requires iodide uptake into the thyrocytes and efflux into the follicular lumen, where it is organified on selected tyrosyls of thyroglobulin. Uptake of iodide into the thyrocytes is mediated by an intrinsic membrane glycoprotein, the sodium-iodide symporter (NIS), which actively cotransports two sodium cations per each iodide anion. NIS-mediated transport of iodide is driven by the electrochemical sodium gradient generated by the Na+/K+-ATPase. NIS is expressed in the thyroid, the salivary glands, gastric mucosa, and the lactating mammary gland. TSH and iodide regulate iodide accumulation by modulating NIS activity via transcriptional and posttranscriptional mechanisms. Biallelic mutations in the NIS gene lead to a congenital iodide transport defect, an autosomal recessive condition characterized by hypothyroidism, goiter, low thyroid iodide uptake, and a low saliva/plasma iodide ratio. Pendrin is an anion transporter that is predominantly expressed in the inner ear, the thyroid, and the kidney. Biallelic mutations in the SLC26A4 gene lead to Pendred syndrome, an autosomal recessive disorder characterized by sensorineural deafness, goiter, and impaired iodide organification. In thyroid follicular cells, pendrin is expressed at the apical membrane. Functional in vitro data and the impaired iodide organification observed in patients with Pendred syndrome support a role of pendrin as an apical iodide transporter. This review shows how the sodium-iodide symporter mediates the active transport of iodide at the basolateral membrane of thyrocytes and discusses biallelic mutations in NIS and the effects of pendrin.

scholarly journals Bone Maturnity Delay in Congenital Hypothyroid

2020 ◽  
Vol 3 (1) ◽  
pp. 726-734
Author(s):  
Azhari Gani ◽  
Iskandar Zakaria
Keyword(s):  
Mental Retardation ◽  
Preterm Birth ◽  
Thyroid Hormone ◽  
Thyroid Gland ◽  
Physical Growth ◽  
Growth Disorders ◽  
Thyroid Dysgenesis ◽  
Thyroid Hormone Biosynthesis ◽  
Age Of Diagnosis ◽  
Hormone Biosynthesis

Congenital hypothyroid (CH) is a Hormonal disorder that can be caused by thyroid gland dysfunction and if not treated early on, will cause serious mental and physical growth disorders. CH is divided into permanent and transient forms which etiologically can be divided into primary, secondary or peripheral. Thyroid dysgenesis is the primary cause and 85% of permanent CH is with abnormalities of thyroid hormone biosynthesis from birth (dishormongeneses). The incidence of dysgenesis accounts for 10-15% of cases. Transient congenital thyroid occurs mostly in infants with preterm birth in low-iodine endemic areas. A study showed a permanent incidence of CH 1: 1500 and transient CH 1: 300 in one of the areas with iodine deficiency in Central Java.Survival analysis showed that the risk of developing mental retardation and delayed physical growth was greater at the age of diagnosis over 1 year.

scholarly journals NADPH oxidases (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

2019 ◽  
Vol 2019 (4) ◽  
Author(s):  
Albert Van der Vliet
Keyword(s):  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Thyroid Hormone ◽  
Thyroid Gland ◽  
Oxygen Species ◽  
Nadph Oxidases ◽  
Thyroid Hormone Biosynthesis ◽  
Production Of Hydrogen ◽  
Nadph Oxidase Complex ◽  
Hormone Biosynthesis

The two DUOX enzymes were originally identified as participating in the production of hydrogen peroxide as a pre-requisite for thyroid hormone biosynthesis in the thyroid gland [6].NOX enzymes function to catalyse the reduction of molecular oxygen to superoxide and various other reactive oxygen species (ROS). They are subunits of the NADPH oxidase complex.

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