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M I N I R E V I E W
Minireview: The Sodium-Iodide Symporter NIS
and Pendrin in Iodide Homeostasis of the Thyroid
Aigerim Bizhanova and Peter Kopp
Division of Endocrinology, Metabolism, and Molecular Medicine, Feinberg School of Medicine, Northwestern
University, Chicago, Illinois 60611
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. (Endocrinology
150: 1084 –1090, 2009)
T
he iodide-containing thyroid hormones T3 and its precursor
T4 are crucial for normal development, growth, and regulation of numerous metabolic pathways. The main function of
the thyroid gland is to concentrate iodide and to make it available
for biosynthesis of thyroid hormones. The significance of this
mechanism is evident in light of the scarcity of iodide in most of
the environment and the fact that insufficient dietary supply of
iodide remains a major public health issue in many parts of the
world (1).
The synthesis of thyroid hormones requires a normally developed thyroid gland, an adequate nutritional intake of iodide,
and a series of sequential biochemical steps. Thyroid hormone
synthesis takes place in the follicles, the functional units of the
gland (2). Each follicle consists of a single layer of thyroid epithelial cells surrounding the follicular lumen. The follicular lumen is filled with colloid, which is predominantly composed of
thyroglobulin, a large glycoprotein that serves as the scaffold for
thyroid hormone synthesis (3).
The synthesis of thyroid hormones requires uptake of iodide
across the basolateral membrane into the thyrocytes, transport
across the cell, and efflux through the apical membrane into the
follicular lumen. Uptake of iodide is mediated by the sodiumiodide symporter (NIS), which cotransports two sodium ions
along with one iodide ion, with the sodium gradient serving as
the driving force (Fig. 1) (1). The energy required to produce the
sodium gradient is provided by the ouabain-sensitive Na⫹/K⫹ATPase (4). The efflux of iodide across the apical membrane is
mediated, at least in part, by pendrin (5). Once iodide reaches the
cell-colloid interface, it is oxidized and rapidly organified by
incorporation into selected tyrosyl residues of thyroglobulin.
This reaction, referred to as organification, is catalyzed by thyroid peroxidase (TPO) in the presence of hydrogen peroxide
and results in the formation of mono- and diiodotyrosines
(MIT and DIT). The generation of hydrogen peroxide is mediated by the calcium-dependent reduced nicotinamide adenine dinucleotide phosphate (NADPH) dual oxidase type 2
ISSN Print 0013-7227 ISSN Online 1945-7170
Printed in U.S.A.
Copyright © 2009 by The Endocrine Society
doi: 10.1210/en.2008-1437 Received October 14, 2008. Accepted January 22, 2009.
First Published Online February 5, 2009
Abbreviations: CICn5, Chloride channel 5; DIT, diiodotyrosine; DUOX2, dual oxidase type
2; ITD, iodide transport defect; MDCK, Madin-Darby canine kidney; MIT, monoiodotyrosine; NIS, sodium-iodide symporter; PKA, protein kinase A; SLC5A, solute carrier 5A; TPO,
thyroperoxidase.
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Endocrinology, March 2009, 150(3):1084 –1090
Follicular lumen
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I
HO -
CH2
I
DIT
HO -
I
I
O
CH2
T3
I
I
HO HO -
CH2
Organification
CH2
MIT
Coupling
TG
TG
HO -
TPO
CH2
TPO
I
TG
HO -
H2O2
I-
CH2
DIT
I
I
HO -
CH2
DIT
I
H2O2
I-
HO -
I
O
I
CH2
T4
I
I
TG
H2O2
I-
nat
di e
TG
d
I-
Io
TG
Apical membrane
TPO
PDS
DUOX2
DUOXA2
NADP+ NADPH
TG
I-
Ca2+
Hydrolysis
DEHAL1
K+
Na+
Na/K-ATPase
2 Na+
NIS
MIT
DIT
T4
T3
I-
?
Basolateral membrane
Na+
FIG. 1. Main steps in thyroid hormone synthesis. At the basolateral membrane
of thyroid follicular cells, which form the follicles, iodide is transported into
thyrocytes by the NIS. NIS is dependent on the sodium gradient created by the
Na/K-ATPase. At the apical membrane, iodide efflux is, in part, mediated by
pendrin (PDS/SLC26A4). At the cell-colloid interface, iodide is oxidized by TPO in
the presence of H2O2. H2O2 is produced by the calcium- and reduced
nicotinamide adenine dinucleotide phosphate-dependent (NADPH) enzyme
DUOX2. DUOX2 requires a specific maturation factor, DUOXA2. Thyroglobulin
(TG), which is secreted into the follicular lumen, serves as matrix for synthesis of
T4 and T3. First, TPO catalyzes iodination of selected tyrosyl residues
(organification), which results in the formation of MIT and DIT. Subsequently,
two iodotyrosines are coupled to form either T4 or T3 in a reaction that is also
catalyzed by TPO. Iodinated thyroglobulin is stored as colloid in the follicular
lumen. Upon a demand for thyroid hormone secretion, thyroglobulin is
internalized into the follicular cell by pinocytosis and digested in lysosomes, which
generates T4 and T3 that are released into the bloodstream through unknown
mechanisms. The unused MIT and DIT are retained in the cell and deiodinated by the
iodotyrosine dehalogenase 1 (DEHAL1). The released iodide is recycled for thyroid
hormone synthesis.
(DUOX2). TPO also catalyzes the coupling of two iodotyrosines to form either T3 or T4. To release thyroid hormones,
thyroglobulin is engulfed by pinocytosis, digested in lysosomes, and then secreted into the bloodstream at the basolateral membrane (2). The mechanisms of hormone secretion
at the basolateral membrane and the involved channel(s) have
not been characterized.
NIS
NIS is an integral plasma membrane glycoprotein localized at the
basolateral plasma membrane of thyrocytes (6). This protein
plays an essential role in thyroid physiology by mediating uptake
of iodide into the thyrocytes, a key step in thyroid hormone
synthesis. The ability of the thyroid gland to accumulate radioiodine is also a cornerstone in the diagnosis and treatment of
thyroid disorders (7).
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The molecular characterization of NIS began in 1996 when
the cDNA encoding rat NIS was isolated by expression-cloning
in Xenopus laevis oocytes (6). Subsequently, the human cDNA
has been cloned by a RT-PCR approach taking advantage of the
homology to rat NIS (8). Rat NIS is predicted to have 618 amino
acids with a relative molecular mass of 65,196 Daltons (6), and
human NIS contains 643 amino acids and exhibits an 84%
amino acid identity and 93% similarity to rat NIS (9). The human NIS gene is located on chromosome 19p12-13.2 and contains 14 introns and 15 exons (9).
NIS (SLC5A5) belongs to the solute carrier family 5A
(SLC5A). All members of this protein family depend on an electrochemical sodium gradient as the driving force for transport of
anions across the plasma membrane (10). The current secondary
structure model predicts that NIS contains 13 transmembrane
domains with the amino terminus located extracellularly and the
carboxy terminus facing the cytosol (1). The mature NIS protein
is approximately 87 kDa in size and has three asparagine-linked
glycosylation sites (1). Glycosylation does not seem to be required for stability, activity, or targeting of the NIS molecule to
the plasma membrane (11). The expression of NIS is differentially regulated and is subjected to various posttranslational
modifications in each tissue in which it is expressed (1, 12).
In addition to thyroid follicular cells, NIS is expressed in several other tissues, including the salivary glands, gastric mucosa,
and the lactating mammary gland, where it mediates active transport of iodide (1). In the lactating mammary gland, NIS plays an
important role by concentrating iodide in the milk, thereby supplying newborns with iodide for thyroid hormone synthesis.
Although NIS has a high affinity for iodide, it is able to mediate transport of other ions (13). Large anions such as thiocyanate and perchlorate can inhibit accumulation of iodide in the
thyroid by competing with iodide (14, 15). Perchlorate is 10 –100
times more potent than thiocyanate in inhibiting iodide accumulation in the thyroid (1). The ability of perchlorate to block
iodide transport has been used in the therapy of hyperthyroidism, and it is used in the perchlorate discharge test, which serves
to detect defects in iodide organification (16). In normal individuals, administration of perchlorate blocks subsequent accumulation of iodide in the thyrocytes but does not cause any discharge of previously accumulated radioiodine because of its
rapid organification. In contrast, in individuals with a total or
partial iodide organification defect, administration of perchlorate results in the rapid release of the unorganified fraction of the
tracer from the thyrocytes (16). Until recently, it has been controversial whether perchlorate acts as a blocker or as a substrate
that is transported by NIS (13, 17, 18). Two recent studies provide evidence that perchlorate is actively transported by NIS (19,
20). Perchlorate transport could be demonstrated in a polarized
cell system (19) as well as by direct measurement with mass
spectrometry (20). Moreover, it has been shown that perchlorate, a widely found pollutant, is transported into the milk (19).
Remarkably, the stoichiometry of the NIS-mediated Na⫹/ClO4⫺
transport is electroneutral, which contrasts with the electrogenic
transport of iodide (two Na⫹ and one I⫺) (19). These findings
indicate that NIS is able to transport different substrates with
distinct stoichiometries (19).
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Bizhanova and Kopp
Minireview
Regulation of NIS protein expression
TSH is the major regulator of thyroid cell proliferation, differentiation, and function, including iodide uptake (21). The effects
of TSH are primarily mediated through the activation of the
cAMP cascade via the GTP-binding protein Gs␣ (22). TSH stimulates iodide accumulation by positively regulating NIS expression at the protein and mRNA level via the cAMP pathway (23).
Hypophysectomized rats with low circulating levels of TSH have
a decreased protein expression of NIS, whereas a single injection
of TSH leads to a prompt increase in NIS expression (24). Rats
maintained on an iodide-deficient diet or treated with propylthiouracil, an agent blocking iodide organification, have high
concentrations of TSH, which correlates with an increase in NIS
protein expression. These findings are in agreement with the
results obtained in human thyroid primary cultures (25, 26) and
the rat thyroid FRTL-5 cell line (23). In FRTL-5 cells, withdrawal
of TSH results in a decrease in intracellular cAMP concentration
and iodide uptake activity (23). Re-addition of TSH increases
NIS mRNA and protein expression and subsequently restores
iodide uptake activity.
Recent studies have shown that TSH not only regulates NIS
transcription and biosynthesis but also mediates NIS activity by
posttranscriptional mechanisms (27). In the presence of TSH,
NIS is active and inserted in the basolateral membrane of thyrocytes (27). Upon TSH withdrawal, NIS protein half-life decreases from 5 to 3 d, and it translocates from the plasma membrane to intracellular compartments (27). As of yet, the
mechanisms regulating the subcellular distribution of NIS are
only partially elucidated. It is known that NIS has several consensus sites for kinases, including protein kinase A (PKA) and
protein kinase C (1). Although it has been shown that NIS is
phosphorylated in vivo (27), the functional significance of this
modification needs further characterization. A more recent study
identified five amino acid residues in NIS that are phosphorylated in vivo, but the phosphorylation status of these amino acid
residues does not affect targeting of NIS to the plasma membrane
(28). NIS contains several sorting sequences that are known to
play a role in targeting, retention, and endocytosis of other membrane proteins (29). For example, the PDZ motif (T/S-X-V/L)
located at the carboxy terminus of NIS is one of the sequences
involved in protein-protein interactions (1). The PDZ motif is
recognized by PDZ-binding proteins that have been implicated in
internalization of other transporters (29). NIS also has a
dileucine motif, L557L558, which is known to interact with the
clathrin-coated system (30). This interaction leads to incorporation of integral membrane proteins into coated vesicles that are
then carried to different destinations within the cell (31).
Iodide is another factor that can regulate iodide accumulation
in the thyroid. In 1948, Wolff and Chaikoff (32) reported that
high doses of iodide block iodide organification in the rat thyroid
in vivo. This phenomenon, known as the acute Wolff-Chaikoff
effect, is a reversible process, because iodide organification resumes when the iodide concentration in the serum decreases. The
mechanisms underlying the Wolff-Chaikoff effect are complex
and involve acute regulation of several key genes and proteins
within the thyrocytes. Several studies have examined the effect of
Endocrinology, March 2009, 150(3):1084 –1090
iodide on NIS mRNA and protein expression in vivo and in vitro
(33–35). In vivo data suggest that high concentrations of iodide
lead to reduction in both NIS mRNA and protein levels, partially
by a transcriptional mechanism. In vitro results suggest that exposure to high doses of iodide results in a decrease in NIS protein
levels that is, at least in part, due to an increase in NIS protein
turnover (33–35).
Congenital iodide transport defect (ITD)
Biallelic mutations in the NIS gene cause a congenital ITD. ITD
is an autosomal recessive condition characterized by hypothyroidism, goiter, reduced or absent thyroid uptake of radioiodide,
and a low saliva/plasma iodide ratio (1, 36). Currently, at least
12 ITD-causing mutations of NIS have been identified (37). Six
of these mutations, namely 226delH, T354P, G395R, Q267E,
G543E, and V59E have been characterized more thoroughly
(38 – 41). The G543E substitution leads to retention of NIS in
intracellular compartments as a result of improper maturation
and trafficking of the protein, the other mutants are still targeted
to the membrane but result in a loss of function (38 – 41). Structural and functional analysis of the T354P mutant protein demonstrated that a hydroxyl group at the ␤-carbon of the residue at
position 354 is crucial for proper NIS function (38). Substitutions of the glycine residue at position 395 residue with several
amino acids indicated that the presence of a small and an uncharged amino acid residue at this position is required for NIS
function (39). Lastly, a recent study revealed that the histidine
residue at position 226 is important for the iodide transport
activity of NIS (37).
Pendrin
Pendrin is a highly hydrophobic membrane protein located at the
apical membrane of thyrocytes (2, 4). In addition to the thyroid,
pendrin is also expressed in the kidney and in the inner ear (42,
43). In the kidney, pendrin plays an important role in acid-base
metabolism as an exchanger of chloride and bicarbonate in ␤-intercalated cells (44). In the inner ear, pendrin is important for
generation of the endocochlear potential (45).
Pendrin belongs to the SLC26A family, which includes several
anion transporters, as well as the motor protein prestin that is
expressed in outer hair cells (46, 47). Pendrin is encoded by the
SLC26A4 gene, which was cloned in 1997 (48). The SLC26A4
gene is located on chromosome 7q21-31 and contains 21 exons
with an open reading frame of 2343 bp (48).
Pendrin is a glycoprotein composed of 780 amino acids (2). It
contains three putative extracellular asparagine-glycosylation
sites (4, 49). Pendrin usually appears as a single protein band
with a molecular mass of 110 –115 kDa when isolated from
human thyroid membranes (49). Pendrin is proposed to have 12
transmembrane domains with both amino and carboxy termini
located inside the cytosol (4, 50). Like other members of the
SLC26A family, pendrin contains a so-called STAS (sulfate
transporter and antisigma factor antagonist) domain (51). The
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Endocrinology, March 2009, 150(3):1084 –1090
exact function of this domain has not been elucidated. Recent
studies, however, suggest that the STAS domain can interact with
the regulatory domain of CFTR (cystic fibrosis transmembrane
conductance regulator) in certain epithelial cells (52–54).
Pendred syndrome
Mutations in the SLC26A4 gene lead to Pendred syndrome (2).
Pendred syndrome is an autosomal recessive disorder characterized by sensorineural deafness, goiter, and a partial defect in
iodide organification (55, 56). Deafness or hearing impairment
is the leading clinical sign of Pendred syndrome (56). In many
patients, hearing loss is prelingual; in some individuals, however,
the hearing loss develops later in childhood (57). Patients with
Pendred syndrome display an enlarged endolymphatic sac and
duct (58 – 60). A subset of patients presents with a so-called
Mondini defect, which is characterized by replacement of the
cochlear turns by a single cavity or a rudimentary cochlea (57,
58). Variability in the hearing loss observed in patients with
SLC26A4 mutations suggests that the phenotype is influenced by
environmental factors and/or genetic modifiers (61).
Goiter usually develops during childhood. There is, however,
a substantial variation within and between families and different
geographic regions (62– 64). Nutritional iodide intake appears
to play an important role as a modifier of the thyroidal phenotype (65, 66). Under conditions of high iodide intake, most individuals have no or only a mild enlargement of the thyroid (60,
67). If the nutritional iodide is scarce, patients with Pendred
syndrome not only develop goiter but may also present with mild
or overt hypothyroidism (68, 69).
Mutations in the SLC26A4 gene, found in patients with Pendred syndrome, are highly heterogeneous (56). Currently, more
than 150 mutations of the SLC26A4 gene have been reported
(56). Most of the mutations are missense mutations, and a
smaller number of mutations consists mainly of nonsense and
intronic mutations (56). Loss of function of some of the mutants
results from the retention of the mutated and misfolded protein
in intracellular compartments, most likely the endoplasmic reticulum (70, 71).
Role of pendrin in the thyroid
Initial functional studies of pendrin in Xenopus oocytes have
demonstrated that pendrin is able to mediate transport of chloride and iodide (5) and that it can act as a chloride/formate
exchanger (72). The ability of pendrin to mediate iodide efflux
(5), the localization of pendrin at the apical membrane of thyrocytes (4, 73), as well as the defect in iodide organification
observed in patients with Pendred syndrome (62, 74), suggested
that pendrin could function as an apical iodide transporter in
thyroid cells (46). The results obtained from a number of independent studies performed in heterologous systems support the
role of pendrin in mediating, at least in part, apical iodide efflux.
Yoshida et al. (75) have demonstrated that iodide efflux is much
higher in nonpolarized Chinese hamster ovary cells expressing
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NIS and pendrin than in cells expressing NIS alone. Electrophysiological studies with transfected COS-7 cells also indicate that
pendrin mediates iodide transport and that it is more efficient at
high extracellular concentrations of chloride (76). In addition,
iodide efflux/chloride influx appears to be more efficient than
chloride efflux/iodide influx (76). These findings are consistent
with results obtained in polarized Madin-Darby canine kidney
(MDCK) cells (50). MDCK cells expressing NIS and pendrin
independently or simultaneously were cultured in a bicameral
system, which allowed measuring iodide uptake at the basolateral membrane and iodide efflux at the apical membrane. Cells
transfected with NIS alone have a significant increase in intracellular iodide uptake compared with untransfected control
cells. In contrast, cells expressing NIS and pendrin show a significant increase in iodide transport into the apical chamber and
consequently a significant decrease in the intracellular iodide
content. These findings support the notion that pendrin may
have a role in facilitating vectorial iodide transport at the apical
membrane (50). The partial organification defect found in patients with Pendred syndrome suggests, however, that iodide can
reach the follicular lumen independently of the presence of
pendrin.
Questions concerning the role of pendrin as
an apical iodide transporter
The traditional concept held that iodide simply crosses the apical
membrane due to the electrochemical gradient that is present
between the cytosol and the follicular lumen (77). However,
autoradiography studies revealed that iodide first accumulates in
the cytosol and subsequently moves to the follicular lumen (78).
This transport of iodide across the apical membrane is rapidly
stimulated by TSH (64, 79). Hence, it has been proposed that
apical iodide efflux is mediated through a specific transporter or
channel. This concept has risen based on several findings. Electrophysiological studies performed with thyroid membrane vesicles suggested the presence of two apical iodide transporters
(80). Functional studies performed in heterologous cells, including polarized cells (50, 75, 76, 81), along with the iodide organification defects found in patients with Pendred syndrome (62,
74), suggested that pendrin mediates apical iodide efflux in thyrocytes. The physiological role of pendrin has, however, been
questioned for several reasons (77). Patients with biallelic mutations in the SLC26A4 gene display a mild or no thyroidal phenotype under conditions of sufficient iodide intake (65). The
pendrin knockout mice, studied under normal iodide intake conditions, do not develop a goiter or abnormal thyroid hormone
levels (45). In addition, it is intriguing that pendrin may have
distinct roles in the thyroid, the inner ear, and the kidney (77).
This led to the proposal that pendrin may be a part of multiprotein complex, the composition of which may vary among different cell types, thereby potentially explaining a variability in anion selectivity of pendrin (77). Other proteins (SLC5A8 and
chloride channel 5 ClCn5) have been proposed to mediate apical
iodide efflux (82, 83). Functional studies performed in Xenopus
oocytes and polarized MDCK cells clearly demonstrate that
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Bizhanova and Kopp
Minireview
SLC5A8, originally designated as human apical iodide transporter (hAIT) (82), does not mediate iodide uptake or efflux (84).
Localization of the ClCn5 protein at the apical membrane of
thyrocytes and a thyroidal phenotype of the ClCn5-deficient
mice that is reminiscent of Pendred syndrome suggest that ClCn5
could be, possibly in conjunction with other chloride channels,
involved in mediating apical iodide efflux or iodide/chloride exchange (83). This possibility has, as of yet, not been corroborated
by further experimental data.
Endocrinology, March 2009, 150(3):1084 –1090
•
•
•
•
Regulation of pendrin expression
TSH stimulates iodide efflux across the apical membrane of thyrocytes (79, 85, 86). After exposure to TSH, iodide efflux is
rapidly stimulated in FRTL-5 cells (85) and in polarized porcine
thyrocytes (79, 86). In polarized porcine thyrocytes grown in a
bicameral system, measurement of iodide transport in both directions demonstrates that TSH up-regulates iodide efflux at the
apical membrane, whereas efflux across the basolateral membrane does not change (79). Treatment of rat thyroid PCCl3 cells
with TSH for a short time results in the rapid translocation of
pendrin from intracellular compartments, specifically endosomes, to the plasma membrane, thus suggesting a role of pendrin in rapid regulation of apical iodide efflux (87). Insertion of
pendrin in the apical membrane correlates with the phosphorylation of pendrin, but it remains unknown whether phosphorylation is necessary or sufficient for this translocation. These
events occur through the PKA pathway and can be inhibited by
H89, a specific PKA inhibitor (87). Interestingly, translocation of
pendrin from the cytosol to the plasma membrane through a
PKC-dependent pathway has been demonstrated after exposure
of cultured rat thyroid cells to insulin for 10, 20, and 40 min (88).
At least in rat FRTL-5 cells, TSH does not significantly modify
SLC26A4 gene expression (4). Interestingly, thyroglobulin has
been shown to up-regulate SLC26A4 mRNA levels in FRTL-5
cells while suppressing expression of several thyroid-specific
genes, including the TSH receptor, NIS, TPO, and TG genes (4).
Treatment with iodide does not affect expression of the
SLC26A4 gene (89). Exposure to thyroglobulin leads to a decreased NIS gene and protein expression and subsequently results in a reduced iodide uptake in vitro (90). In contrast, accumulation of thyroglobulin in the follicular lumen suppresses
iodide uptake in vivo (90). It has been suggested that the inverse
relationship between the concentration of thyroglobulin in the
follicular lumen and iodide uptake in vivo may be important in
the regulation of thyroid function under constant TSH levels (91)
and promote iodide efflux into the follicular lumen (89).
Conclusions
• NIS mediates the active transport of iodide at the basolateral
membrane of thyrocytes.
• Biallelic mutations in NIS cause a congenital iodide transport
defect, an autosomal recessive condition, characterized by hy-
•
pothyroidism, goiter, low thyroid iodide uptake, and low saliva/plasma iodide ratio.
Pendrin is involved in the apical iodide efflux in thyroid cells.
It can also exchange chloride and bicarbonate.
Pendrin is encoded by the SLC26A4 gene. Biallelic mutations
in the SLC26A4 gene cause Pendred syndrome, an autosomal
recessive disorder, characterized by deafness, goiter, and impaired iodide organification.
In the inner ear, pendrin is important for anion and fluid
transport and for maintenance of the endocochlear potential.
In the kidney, pendrin plays a role in acid-base metabolism as
a chloride/bicarbonate exchanger.
In addition to pendrin, other apical iodide channels or transporters may be involved in regulation of apical iodide efflux
in thyrocytes.
Acknowledgments
Address all correspondence and requests for reprints to: Peter Kopp,
M.D., Associate Professor, Director ad interim Center of Genetic Medicine, Division of Endocrinology, Metabolism, and Molecular Medicine,
Northwestern University, Tarry 15, 303 East Chicago Avenue, Chicago,
Illinois 60611. E-mail: [email protected].
Part of this work has been supported by Grant 1R01DK63024-01
from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (to P.K.).
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