title: Dietary I(-) absorption: expression and regulation of the Na(+)/I(-) symporter in the intestine.
abstract: Thyroid hormones are critical for the normal development, growth, and functional maturation of several tissues, including the central nervous system. Iodine is an essential constituent of the thyroid hormones, the only iodine-containing molecules in vertebrates. Dietary iodide (I(-)) absorption in the gastrointestinal tract is the first step in I(-) metabolism, as the diet is the only source of I(-) for land-dwelling vertebrates. The Na(+)/I(-) symporter (NIS), an integral plasma membrane glycoprotein located in the brush border of enterocytes, constitutes a central component of the I(-) absorption system in the small intestine. In this chapter, we review the most recent research on structure/function relations in NIS and the protein's I(-) transport mechanism and stoichiometry, with a special focus on the tissue distribution and hormonal regulation of NIS, as well as the role of NIS in mediating I(-) homeostasis. We further discuss recent findings concerning the autoregulatory effect of I(-) on I(-) metabolism in enterocytes: high intracellular I(-) concentrations in enterocytes decrease NIS-mediated uptake of I(-) through a complex array of posttranscriptional mechanisms, e.g., downregulation of NIS expression at the plasma membrane, increased NIS protein degradation, and reduction of NIS mRNA stability leading to decreased NIS mRNA levels. Since the molecular identification of NIS, great progress has been made not only in understanding the role of NIS in I(-) homeostasis but also in developing protocols for NIS-mediated imaging and treatment of various diseases.
authors.affiliation: Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Nicola
authors.affiliation: Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut, USA. Electronic address: nancy.carrasco@yale.edu.
authors.forename: Nancy
authors.initials: N
authors.lastname: Carrasco
authors.affiliation: Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina. Electronic address: amasini@fcq.unc.edu.ar.
authors.forename: Ana María
authors.initials: AM
authors.lastname: Masini-Repiso
mesh_terms: D004032:Diet; D015536:Down-Regulation; D020895:Enterocytes / Q000378:metabolism; D065569:Gastrointestinal Absorption / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology; D007454:Iodides / Q000008:administration & dosage / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D013961:Thyroid Gland / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism; D000099209:Sodium-Iodide Symporters
chemical_list: D007454:Iodides; D012333:RNA, Messenger; D027981:Symporters; D013963:Thyroid Hormones; D000099209:Sodium-Iodide Symporters
keywords: 3′-Untranslated region; Brush border; Dietary iodide absorption; Iodide; Iodide deficiency disorders; Na(+)/I(−) symporter; Posttranscriptional regulation; Small intestine; Thyroid hormones