Development of a screening approach to detect thyroid disrupting chemicals that inhibit the human sodium iodide symporter (NIS)

Hallinger, Daniel R.; Murr, Ashley S.; Buckalew, Angela R.; Simmons, Steven O.; Stoker, Tammy E.; Laws, Susan C.

doi:10.1016/j.tiv.2016.12.006

Cited by 71 publications

(52 citation statements)

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“…The IC 50 values for perchlorate were determined as follows: hNIS: 1.566 μM, wNIS: 4.599 μM, zNIS: 0.081 μM (Fig 5). The value obtained for hNIS is similar to other reported values of 0.488 μM and 1.27 μM [83,84].…”

Section: Perchlorate Ic 50 Determination For Human- Minke Whale- Ansupporting

confidence: 91%

“…The mechanism by which NIS transports its various monovalent anionic substrates remains poorly understood. NIS does not transport every monovalent anion and it is still unclear what differentiates a substrate from an inhibitor or irrelevant anion [13,[83][84][85][86][87]. Here we compared the anion selectivity and inhibitor sensitivity of NIS proteins from diverse animal species and found, unexpectedly, that they differ not only in their ability to transport the NIS substrates 99m , but also in their susceptibilities to inhibition of iodide transport by a wide range of monovalent anions.…”

Section: Discussionmentioning

confidence: 84%

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Inter-species variation in monovalent anion substrate selectivity and inhibitor sensitivity in the sodium iodide symporter (NIS)

et al. 2020

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Section: Perchlorate Ic 50 Determination For Human- Minke Whale- Ansupporting

confidence: 91%

Section: Discussionmentioning

confidence: 84%

Inter-species variation in monovalent anion substrate selectivity and inhibitor sensitivity in the sodium iodide symporter (NIS)

et al. 2020

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“…by evaluating in vitro the potential for inhibition of the sodium-iodide symporter (NIS) (Cianchetta et al, 2010;Kogai and Brent, 2012;Hallinger et al, 2017) and thyroid peroxidase (TPO) (Kambe and Seo, 1997;Paul et al, 2014;Paul Friedman et al, 2016;Wu et al, 2016). by evaluating in vitro the potential for inhibition of the sodium-iodide symporter (NIS) (Cianchetta et al, 2010;Kogai and Brent, 2012;Hallinger et al, 2017) and thyroid peroxidase (TPO) (Kambe and Seo, 1997;Paul et al, 2014;Paul Friedman et al, 2016;Wu et al, 2016).…”

Section: Sorting the Ass In The Cag For Hypothyroidism Per Moamentioning

confidence: 99%

“…3) The presence of other possible thyroid-disrupting modes of action such as interference with TH synthesis should also be excluded, e.g. by evaluating in vitro the potential for inhibition of the sodium-iodide symporter (NIS) (Cianchetta et al, 2010;Kogai and Brent, 2012;Hallinger et al, 2017) and thyroid peroxidase (TPO) (Kambe and Seo, 1997;Paul et al, 2014;Paul Friedman et al, 2016;Wu et al, 2016). It must, however, be acknowledged that substances may interfere with the thyroid hormone system through many different mechanisms of action, and that currently validated/standardised in vitro assays do not exist to investigate all these different pathways and a reasonable effort is anticipated, based on available tools and current understanding of thyroid physiology'.…”

Section: Liver Enzyme Inductionmentioning

confidence: 99%

Establishment of cumulative assessment groups of pesticides for their effects on the thyroid

Crivellente¹,

Hart²,

Hernández‐Jerez³

et al. 2019

EFS2

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Cumulative assessment groups of pesticides have been established for two specific effects on the thyroid: firstly hypothyroidism, and secondly parafollicular cell (C-cell) hypertrophy, hyperplasia and neoplasia. Sources of uncertainties resulting from the methodological approach and from the limitations in available data and scientific knowledge have been identified and considered. This report supports the publication of a scientific report on cumulative risk assessment to pesticides affecting the thyroid, in which all uncertainties identified for either the exposure assessment or the establishment of the cumulative assessment groups are incorporated into a consolidated risk characterisation.

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“…Others have been shown to activate the nuclear receptors pregnane X receptor (PXR), constitutive androstane receptor (CAR) (Kretschmer and Baldwin 2005), or arylhydrocarbon receptor (AhR) (Denison and Nagy 2003), thereby inducing the expression and activity of uridine diphosphate glucuronosyltransferase (UGT) isoforms 1A1 and 1A6 (Shelby and Klaassen 2006), which are responsible for an increased glucuronidation (Roos et al 2011;Vansell and Klaassen 2002) and subsequent hepatic clearance (Liu et al 1995) of TH. Still others have been shown to inhibit the sodium iodide symporter (NIS) (Hallinger et al 2017;Wang et al 2018) or thyroid peroxidase (TPO) (Paul et al 2014), which are involved in TH synthesis. In the present study, we focus on the TH distributor protein transthyretin (TTR) as a target for TH disrupting compounds.…”

Section: Introductionmentioning

confidence: 99%

Transthyretin-Binding Activity of Complex Mixtures Representing the Composition of Thyroid-Hormone Disrupting Contaminants in House Dust and Human Serum

Hamers

Kortenkamp

Scholze

et al. 2020

Environ Health Perspect

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BACKGROUND: House dust contains many organic contaminants that can compete with the thyroid hormone (TH) thyroxine (T 4 ) for binding to transthyretin (TTR). How these contaminants work together at levels found in humans and how displacement from TTR in vitro relates to in vivo T 4 -TTR binding is unknown. OBJECTIVES: Our aims were to determine the TTR-binding potency for contaminant mixtures as found in house dust, maternal serum, and infant serum; to study whether the TTR-binding potency of the mixtures follows the principle of concentration addition; and to extrapolate the in vitro TTRbinding potency to in vivo inhibition levels of T 4 -TTR binding in maternal and infant serum. METHODS: Twenty-five contaminants were tested for their in vitro capacity to compete for TTR-binding with a fluorescent FITC-T 4 probe. Three mixtures were reconstituted proportionally to median concentrations for these chemicals in house dust, maternal serum, or infant serum from Nordic countries. Measured concentration-response curves were compared with concentration-response curves predicted by concentration addition. For each reconstituted serum mixture, its inhibitor-TTR dissociation constant (K i ) was used to estimate inhibition levels of T 4 -TTR binding in human blood. RESULTS: The TTR-binding potency of the mixtures was well predicted by concentration addition. The ∼ 20% inhibition in FITC-T 4 binding observed for the mixtures reflecting median concentrations in maternal and infant serum was extrapolated to 1.3% inhibition of T 4 -TTR binding in maternal and 1.5% in infant blood. For nontested mixtures reflecting high-end serum concentrations, these estimates were 6.2% and 4.9%, respectively. DISCUSSION: The relatively low estimated inhibition levels at median exposure levels may explain why no relationship between exposure to TTRbinding compounds and circulating T 4 levels in humans has been reported, so far. We hypothesize, however, that 1.3% inhibition of T 4 -TTR binding may ultimately be decisive for reaching a status of maternal hypothyroidism or hypothyroxinemia associated with impaired neurodevelopment in children. https://doi.

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Development of a screening approach to detect thyroid disrupting chemicals that inhibit the human sodium iodide symporter (NIS)

Cited by 71 publications

References 50 publications

Inter-species variation in monovalent anion substrate selectivity and inhibitor sensitivity in the sodium iodide symporter (NIS)

Inter-species variation in monovalent anion substrate selectivity and inhibitor sensitivity in the sodium iodide symporter (NIS)

Establishment of cumulative assessment groups of pesticides for their effects on the thyroid

Transthyretin-Binding Activity of Complex Mixtures Representing the Composition of Thyroid-Hormone Disrupting Contaminants in House Dust and Human Serum

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