Erik R. Janus; M3 Technical & Regulatory Services; Shepherdstown, WV; <firstname.lastname@example.org>
Kristie Sullivan; Physicians Committee for Responsible Medicine; Washington, DC; <email@example.com>
Katie Paul-Friedman; US Environmental Protection Agency; Research Triangle Park, NC
Mary Gilbert; National Health and Environmental Effects Research Laboratory; US Environmental Protection Agency; Research Triangle Park, NC; <firstname.lastname@example.org>
Kevin M. Crofton; National Center for Computational Toxicology; US Environmental Protection Agenc; Research Triangle Park, NC; <email@example.com>
Point of Contact
- Erik Janus
|Author status||OECD status||OECD project||SAAOP status|
|Under development: Not open for comment. Do not cite||Under Development||1.41||Included in OECD Work Plan|
This AOP was last modified on March 20, 2017 09:47
|Binding, Transthyretin in serum||September 16, 2017 10:16|
|Displacement, Serum thyroxine (T4) from transthyretin||December 17, 2016 17:03|
|Increased, Free serum thyroxine (T4)||September 16, 2017 10:16|
|Increased, Uptake of thyroxine into tissue||December 17, 2016 17:04|
|Increased, Clearance of thyroxine from tissues||September 16, 2017 10:16|
|Thyroxine (T4) in serum, Decreased||September 17, 2017 18:37|
|Thyroxine (T4) in neuronal tissue, Decreased||September 17, 2017 17:11|
|Hippocampal gene expression, Altered||September 17, 2017 17:14|
|Hippocampal anatomy, Altered||September 16, 2017 10:14|
|Hippocampal Physiology, Altered||September 17, 2017 17:17|
|Cognitive Function, Decreased||April 16, 2017 13:45|
|Halogenated phenols||March 09, 2017 23:55|
|Polychlorinated biphenyl||November 29, 2016 18:42|
|Polychlorinated dibenzodioxins||March 09, 2017 20:38|
|Polybrominated diphenyl ethers||March 09, 2017 20:40|
|Isoflavones||March 09, 2017 21:14|
|Perflourinated chemicals||March 09, 2017 22:36|
|Phthalates||March 09, 2017 22:37|
|Tetrabromobisphenol A||March 10, 2017 00:10|
|Clonixin||March 10, 2017 00:50|
|Meclofenamic acid||March 10, 2017 00:51|
|2,6-dinitro-p-cresol||March 10, 2017 00:53|
|Triclopyr||March 10, 2017 00:59|
|2,2',4,4'-Tetrahydroxybenzophenone||November 29, 2016 18:42|
This AOP describes adverse neurodevelopemental effects that may result from xenobiotic interference with thyroid serum binding protein transthyretin (TTR). Binding of TTR by a xenobiotic (the MIE) during certain developmental windows may disrupt the normal neurodevelopment of mammals through a transient increase in free thyroxine (T4) levels, permitting increased tissue uptake of thyroid hormone (TH), followed by a decrease in both serum and neuronal tissue concentrations. Due to the highly conserved nature of the TTR protein, birds, reptiles, fish and amphibians can also express TTR and be impacted by interference by xeniobiotics. The adverse consequences of TH insufficiency depend both on the severity and developmental timing, indicating that exposure to thyroid toxicants may produce different effects at different developmental windows of exposure. This AOP discusses the potential for developmental TTR interference to adversely impact hippocampal anatomy, function, gene expression and, ultimately, cognitive function.
Transthyretin is one of three ancient, highly conserved serum binding proteins that collectively act to transport thyroid hormone (TH) and thus help maintain normal homeostasis via modulation of the hypothalamic/pituitary/thyroid axis. In addition to TTR, albumin (ALB) and thyroxine-binding globulin (TBG) also serve to transport TH in serum and the relative contribution of each binding protein differs across species. In man, TBG has the greatest affinity for thyroxine (T4), followed by TTR and ALB shows the lowest affinity for T4 while prevalence in serum is the opposite, while in rat, TTR is the major serum transport protein (as rats lack TBG). Interference with TH serum binding proteins is one of several mechanisms through which xenobiotics and environmental contaminants can disrupt normal thyroid endocrine function ("thyroid disruptors") and development of this AOP is expected to contribute towards a fuller understanding of the mechanism of TTR interference and how it may be measured in vitro as part of a larger screening battery for thyroid toxicants.
Summary of the AOP
|Polychlorinated dibenzodioxins||Not Specified|
|Polybrominated diphenyl ethers||Strong|
|Tetrabromobisphenol A||Not Specified|
|Meclofenamic acid||Not Specified|
Molecular Initiating Event
|Binding, Transthyretin in serum||Binding, Transthyretin in serum|
|Displacement, Serum thyroxine (T4) from transthyretin||Displacement, Serum thyroxine (T4) from transthyretin|
|Increased, Free serum thyroxine (T4)||Increased, Free serum thyroxine (T4)|
|Increased, Uptake of thyroxine into tissue||Increased, Uptake of thyroxine into tissue|
|Increased, Clearance of thyroxine from tissues||Increased, Clearance of thyroxine from tissues|
|Thyroxine (T4) in serum, Decreased||T4 in serum, Decreased|
|Thyroxine (T4) in neuronal tissue, Decreased||T4 in neuronal tissue, Decreased|
|Hippocampal gene expression, Altered||Hippocampal gene expression, Altered|
|Hippocampal anatomy, Altered||Hippocampal anatomy, Altered|
|Hippocampal Physiology, Altered||Hippocampal Physiology, Altered|
|Cognitive Function, Decreased||Cognitive Function, Decreased|
Relationships Between Two Key Events (Including MIEs and AOs)The utility of AOPs for regulatory application is defined to a large extent by the confidence and precision with which they facilitate extrapolation of data measured at low levels of biological organization to predicted outcomes at higher levels of organization and the extent to which they can link biological effect measurements to their specific causes. Within the AOP framework, the predictive relationships that facilitate extrapolation are represented by the KERs. Consequently, the overall weight of evidence for an AOP is a reflection in part, of the level of confidence in the underlying series of KERs it encompasses. Therefore, describing the KERs in an AOP involves assembling and organising the types of information and evidence that defines the scientific basis for inferring the probable change in or state of a downstream KE from the known or measured state of an upstream KE. Description of the scientific evidence supporting KERs in an AOP is an important step in the AOP development process that sets the stage for assessment of the AOP (section 7). The modified Bradford Hill considerations of biological plausibility and empirical support can be evaluated with regard to the predictive relationships/associations between pairs of KEs as a basis for considering weight of evidence of KERs (Section 7). The plausibility of the relationship between two KEs with respect to current understanding of normal (i.e., unperturbed biology) can be evaluated. Concordance of empirical evidence (i.e., dose-response, temporal and incidence concordance) can also be assessed and is usually based on consideration of these relationships following exposure to specific stressors that are believed to initiate the pathway. For example, temporal concordance can be evaluated by considering whether each “upstream” KE precedes the next “downstream” KE in the series. For empirical evidence derived for a specific stressor, dose-response and incidence concordance can also be evaluated to determine whether the pattern of results supports the hypothesized KER – i.e., does KEupstream occur at equivalent or lower doses and/or with less frequency than KEdownstream. Consistencies or inconsistencies in supporting data across different biological contexts and/or multiple studies can also help define confidence in the KER. Therefore, the suggested subsections of the KER description included in the current template are intended to aid the user in collecting relevant information that will support evaluation of the level of confidence in each KER, which in turn contributes to the assessment of the weight of evidence of the AOP, overall (section 7). By convention, KERs may take one of two forms. They may refer specifically to direct linkage between a pair of KEs that are adjacent in an AOP. Alternatively, a KER may refer to indirect linkages between a pair of KEs for which the relationship is thought to run through another KE or a gap in current understanding (i.e., non-adjacent KEs in an AOP; represented as dashed arrows in Figure 3). It is not necessary to describe a KER for every possible binary pair of KEs that could be indirectly linked. However, the option to provide KER descriptions for indirect KERs is particularly useful within the AOP-Wiki, because empirical evidence supporting the linkages among KEs in an AOP (see below) may often skip steps. For example, some KE measurements may be fairly difficult to make, such that they are rarely made in routine studies. While there may be sufficient data to establish the KE as part of the AOP, much of the available weight of evidence may ignore or “leap over” that particular KE. Including indirect KER descriptions allows the weight of evidence for these indirect relationships to be readily described and linked to other AOPs. Additionally, it can aid the process of developing and expanding putative AOPs where initial 19 linkages may span significant knowledge-gaps which are later filled in with additional KEs as more information becomes available and/or targeted research is completed. Instructions To add a key event relationship to an AOP page, under Summary of the AOP, next to “Relationships Between Two Key Events (Including MIEs and AOs)” click ‘Add relationship.’ User will be brought to a new page entitled ‘Add Relationship to AOP.’ To create a new relationship, select an upstream event and a downstream event from the drop down menus. Select a Directness from the drop down menu. The fields “Evidence” and “Quantitative understanding” can be entered at the time of creation of the relationship, or can be added later. Upon selection of these options from their respective drop-down menus, click ‘Update Aop relationship.’ The new relationship should be listed on the AOP page. To edit a key event relationship, click ‘Edit’ next to the name of the relationship you wish to edit. The user will be directed to an Editing Relationship page where they can edit the Directness, Evidence, and Quantitative Understanding fields using the drop down menus. Once finished editing, click ‘Update Aop relationship’ to update these fields and return to the AOP page.
Life Stage ApplicabilityIs the AOP specific to certain tissues, life stages / age classes? Indicate if there are critical life stages, where exposure must occur, to results in the final adverse effect. Or specify if there are key events along the pathway which are dependent on the life stage although the AOP is known to be initiated regardless of life stage. Indicate also if the AOP is associated also with age- or sex-dependence. Instructions To add a life stage term to an AOP page, under “Life Stage Applicability” select ‘add life stage term.’ User will be directed to a page entitled “Add Life Stage to AOP.” This page will list the AOP name, with drop down menu options to select a Life Stage term and Evidence. Evidence can be left blank and added later. To edit a life stage term on an AOP page, under “Life Stage Applicability” click ‘Edit.’ User will be directed to a page entitled “Editing AOP Life Stage” where they can edit the Evidence field using the drop down menu. Clicking ‘Update Aop life stage’ will update the Evidence field and redirect the user back to the AOP page.
Taxonomic ApplicabilityIndicate the relevant domain of applicability in terms of taxa. Instructions To add a taxonomic term to an AOP page, under “Taxonomic Applicability” select ‘add taxonomic term.’ User will be directed to a page entitled “Adding Taxonomic Term to AOP.” The user can search for and select an existing term from the drop down list of existing terms to populate the “Term” field. If a relevant term does not exist, click ‘Request New Taxon Term’ to request a term from AOP-Wiki administrators. Click ‘Add taxonomic term’ to add this term to the AOP page. Evidence can be left blank and added later. To edit a taxonomic term on an AOP page, under “Taxonomic Applicability” click ‘Edit.’ User will be directed to a page entitled “Editing AOP Taxonomic Term” where they can edit the Evidence field using the drop down menu. Clicking ‘Update taxonomic term’ will update the Evidence field and redirect the user back to the AOP page.
Graphical RepresentationClick to download graphical representation template
Overall Assessment of the AOP
This section addresses the relevant domain of applicability (i.e., in terms of taxa, sex, life stage, etc.) and weight of evidence for the overall hypothesised AOP (i.e., including the MIE, KEs and AO) as a basis to consider appropriate regulatory application (e.g., priority setting, testing strategies or risk assessment). It draws upon the evidence assembled for each KER as one of several components which contribute to relative confidence in supporting information for the entire hypothesised pathway. An important component in assessing confidence in supporting information as a basis to consider regulatory application of AOPs beyond that described in Section 6 is the essentiality of each of the key events as a component of the entire pathway. This is normally investigated in specifically-designed stop/reversibility studies or knockout models (i.e., those where a key event can be blocked or prevented). Assessment of the overall AOP also contributes to the identification of KEs for which confidence in the quantitative relationship with the AO is greatest (i.e., to facilitate determining the most sensitive predictor of the AO). Instructions To edit the “Overall Assessment of the AOP” section, on an AOP page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing AOP.” Scroll down to the “Overall Assessment of the AOP” section, where a text entry box allows you to submit text. In the upper right hand menu, click ‘Update AOP’ to save your changes and return to the AOP page. The new text should appear under the “Overall Assessment of the AOP” section on the AOP page.
Domain of ApplicabilityThe relevant domain(s) of applicability in terms of sex, life-stage, taxa, and other aspects of biological context are defined in this section. Domain of applicability is informed by the “Description” and “Taxonomic Relevance” section of each KE description and the “Description of the KER” section of each KER description. The relevant domain of applicability of the AOP as a whole will most often be defined based on the most narrowly restricted of its KEs. For example, if most of the KEs apply to either sex, but one is relevant to females only, the domain of applicability of the AOP as a whole would generally be limited to females. While much of the detail defining the domain of applicability may be found in the individual KE descriptions, the rationale for defining the relevant domain of applicability of the overall AOP should be briefly summarised on the AOP page. Instructions To edit the “Domain of Applicability” section, on an AOP page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing AOP.” Scroll down to the “Domain of Applicability” section, where a text entry box allows you to submit text. In the upper right hand menu, click ‘Update AOP’ to save your changes and return to the AOP page. The new text should appear under the “Domain of Applicability” section on the AOP page.
Essentiality of the Key Events
Molecular Initiating Event Summary, Key Event Summary
Provide an overall assessment of the essentiality for the key events in the AOP. Support calls for individual key events can be included in the molecular initiating event, key event, and adverse outcome tables above.
In vivo evidence for MIE
Kohrle et al (1989) added 10 μmol/L 3-methyl-4’,6-dihydroxy-3’,5-dibromo-flavone (EMD 21388) to pooled rat serum and measured displacement of [125I]-T4 from TTR. EMD21388 was synthesized using “molecular drug design” (and resembles T4) to help confirm previous findings that certain flavonoid deiodinase inhibitors also displaced thyroxine (T4) for TTR (or T3-binding prealbumin). Displacement of [125I] from TTR in rat serum was analyzed by gel electrophoresis (PAGE) and individual serum samples were assayed for T3 and T4 content by RIA and % free TH by equilibrium dialysis (lower limit of detectability 0.3 ug/dL for T4). There was a significant increase in % free T4 (0.031 to 0.124), which was dose-dependent and resulted in complete inhibition of [125I]-T4/TTR at 8-10 umol (radiolabeled TH were displaced primarily to albumin).
One to 4 hours following ip delivery of 2 μmol/100 g BW to euthyroid Sprague-Dawley rats (a dose that is 1000x higher than daily T4 production in rat), inhibition of [125I]-T4/TTR binding was observed. T4 decreased from 5.6 to 2.3 ug/dl after 1 hour and remained low while % free T4 increased from 0.035 to 0.091 and remained high; however, free T4 did not change. TSH decreased to very low values after 2 hours and increased slightly, despite no change in the free TH concentration (hypothyroid rats did not show changes in serum TSH following EMD 21388 administration). Lueprasitsakul et al (1990) performed a series of experiments with Sprague-Dawley rats using smaller doses of EMD 21388 (up to 2 μmol /100 g BW) and the same measurement methods (RIA, equilibrium dialysis). Administration of 2 μmol of EMD 21388 inhibited [125I]-T4/TTR binding within a few minutes, displacing [125I] to albumin to a greater degree of magnitude, due to slight differences in preparing the EMD 21388 solutions. Dose-dependent decreases in displacement were found with decreasing dose.
Following a single dose of 2 μmol, a significant decrease was seen in total serum T4 after 10 minutes that persisted, % free T4 also increased immediately (peaked after 10 minutes) and stayed elevated and a significant increase in free T4 was observed within three minutes that stayed elevated for 60 minutes. Following a single dose of 0.3 μmol, decreased [125I]-T4/TTR binding was observed reaching a nadir after 10 minutes and slowly recovering over the 180-minute experiment. The % free T4 and serum free T4 both increased and returned to normal after 180 minutes as well while total serum T4 hit a nadir after 10 minutes and mostly recovered. Serum TSH decreased after 20 minutes, significantly at the nadir hit after 60 minutes.
Weight of Evidence SummaryThis involves evaluation of the Overall AOP based on Relative Level of Confidence in the KERs, Essentiality of the KEs and Degree of Quantitative Understanding based on Annexes 1 and 2. Annex 1 (“Guidance for assessing relative level of confidence in the Overall AOP”) guides consideration of the weight of evidence or degree of confidence in the predictive relationship between pairs of KEs based on KER descriptions and support for essentiality of KEs. It is designed to facilitate assignment of categories of high, moderate or low against specific considerations for each a series of defined element based on current experience in assessing MOAs/AOPs. In addition to increasing consistency through delineation of defining questions for the elements and the nature of evidence associated with assignment to each of the categories, importantly, the objective of completion of Annex 1 is to transparently delineate the rationales for the assignment based on the specified considerations. While it is not necessary to repeat lengthy text which appears in earlier parts of the document, the entries for the rationales should explicitly express the reasoning for assignment to the categories, based on the considerations for high, moderate or low weight of evidence included in the columns for each of the relevant elements. 24 While the elements can be addressed separately for each of the KERs, the essentiality of the KEs within the AOP is considered collectively since their interdependence is often illustrated through prevention or augmentation of an earlier or later key event. Where it is not possible to experimentally assess the essentiality of the KEs within the AOP (i.e., there is no experimental model to prevent or augment the key events in the pathway), this should be noted. Identified limitations of the database to address the biological plausibility of the KERs, the essentiality of the KEs and empirical support for the KERs are influential in assigning the categories for degree of confidence (i.e., high, moderate or low). Consideration of the confidence in the overall AOP is based, then, on the extent of available experimental data on the essentiality of KEs and the collective consideration of the qualitative weight of evidence for each of the KERs, in the context of their interdependence leading to adverse effect in the overall AOP. Assessment of the overall AOP is summarized in the Network View, which represents the degree of confidence in the weight of evidence both for the rank ordered elements of essentiality of the key events and biological plausibility and empirical support for the interrelationships between KEs. The AOP-Wiki provides such a network graphic based on the information provided in the MIE, KE, AO, and KER tables. The Key Event Essentiality calls are used to determine the size of each key event node with larger sizes representing higher confidence for essentiality. The Weight of Evidence summary in the KER table is used to determine the width of the lines connecting the key events with thicker lines representing higher confidence. Instructions To edit the “Weight of Evidence Summary” section, on an AOP page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing AOP.” Scroll down to the “Weight of Evidence Summary” section, where a text entry box allows you to submit text. In the upper right hand menu, click ‘Update AOP’ to save your changes and return to the AOP page. The new text should appear under the “Weight of Evidence Summary” section on the AOP page.
Quantitative ConsiderationsThe extent of quantitative understanding of the various KERs in the overall hypothesised AOP is also critical in consideration of potential regulatory application. For some applications (e.g. doseresponse analysis in in depth risk assessment), quantitative characterisation of downstream KERs may be essential while for others, quantitative understanding of upstream KERs may be important (e.g., QSAR modelling for category formation for testing). Because evidence that contributes to quantitative understanding of the KER is generally not mutually exclusive with the empirical support for the KER, evidence that contributes to quantitative understanding should generally be considered as part of the evaluation of the weight of evidence supporting the KER (see Annex 1, footnote b). General guidance on the degree of quantitative understanding that would be characterised as weak, moderate, or strong is provided in Annex 2. Instructions To edit the “Quantitative Considerations” section, on an AOP page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing AOP.” Scroll down to the “Quantitative Considerations” section, where a text entry box allows you to submit text. In the upper right hand menu, click ‘Update AOP’ to save your changes and return to the AOP page. The new text should appear under the “Quantitative Considerations” section on the AOP page.
Considerations for Potential Applications of the AOP (optional)
At their discretion, the developer may include in this section discussion of the potential applications of an AOP to support regulatory decision-making. This may include, for example, possible utility for test guideline development or refinement, development of integrated testing and assessment approaches, development of (Q)SARs / or chemical profilers to facilitate the grouping of chemicals for subsequent read-across, screening level hazard assessments or even risk assessment. While it is challenging to foresee all potential regulatory application of AOPs and any application will ultimately lie within the purview of regulatory agencies, potential applications may be apparent as the AOP is being developed, particularly if it was initiated with a particular application in mind. This optional section is intended to provide the developer with an opportunity to suggest potential regulatory applications and describe his or her rationale. Detailing such considerations can aid the process of transforming narrative descriptions of AOPs into practical tools. In this context, it is necessarily beneficial to involve members of the regulatory risk assessment community on the development and assessment team. The Network view which is generated based on assessment of weight of evidence/degree of confidence in the hypothesized AOP taking into account the elements described in Section 7 provides a useful summary of relevant information as a basis to consider appropriate application in a regulatory context. Consideration of application needs then, to take into consideration the following rank ordered qualitative elements: Confidence in biological plausibility for each of the KERs Confidence in essentiality of the KEs Empirical support for each of the KERs and overall AOP The extent of weight of evidence/confidence in both these qualitative elements and that of the quantitative understanding for each of the KERs (e.g., is the MIE known, is quantitative understanding restricted to early or late key events) is also critical in determining appropriate application. For example, if the confidence and quantitative understanding of each KER in a hypothesised AOP are low and or low/moderate and the evidence for essentiality of KEs weak (Section 7), it might be considered as appropriate only for applications with less potential for impact (e.g., prioritisation, category formation for testing) versus those that have immediate implications potentially for risk management (e.g., in depth assessment). If confidence in quantitative understanding of late key events is high, this might be sufficient for an in depth assessment. The analysis supporting the Network view is also essential in identifying critical data gaps based on envisaged regulatory application. Instructions To edit the “Considerations for Potential Applications of the AOP” section, on an AOP page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing AOP.” Scroll down to the “Considerations for Potential Applications of the AOP” section, where a text entry box allows you to submit text. In the upper right hand menu, click ‘Update AOP’ to save your changes and return to the AOP page. The new text should appear under the “Considerations for Potential Applications of the AOP” section on the AOP page.
Abdalla, S.M. and A.C. Bianco. (2014) Defending plasma T3 is a biological priority. Clin. Endocrinol. (Oxf) 81(5): 633-641.
Alshehri, B., D’Souza, D. G., Lee, J. Y., Petratos, S., & Richardson, S. J. (2015). The Diversity of Mechanisms Influenced by Transthyretin in Neurobiology: Development, Disease and Endocrine Disruption. Journal of Neuroendocrinology, 27(5), 303–323. http://doi.org/10.1111/jne.12271
Andrea, T.A., R.R. Cavalieri, I.D. Goldfine and E.C. Jorgensen (1980) Binding of thyroid hormones and analogues to the human plasma protein prealbumin. Biochemistry 19(1): 55-63.
Aqai, P., C. Fryganas, M. Mizuguchi, W. Haasnoot and M.W. Nielen. (2012) Triple bioaffinity mass spectrometry concept for thyroid transporter ligands. Anal. Chem. 84(15): 6488-6493.
Athanasiadou, M., S.N. Cuadra, G. Marsh, A> Bergman, and K. Jakobsson. (2008) Polybrominated diphenyl ethers (PBDEs) and bioaccumulative hydroxylated PBDE metabolites in young humans from Managua, Nicaragua. Environ. Health Perspect. 116(3): 400-408.
Barter, R.A. and C.D. Klaassen. (1994) Reduction of thyroid hormone levels and alteration of thyroid function by four representative UDP-glucuronosyltransferase inducers in rats. Toxicol. Appl. Pharmacol. 128(1): 9-17.
Blake, C.C., J.M. Burridge and S.J. Oatley. (1978) X-ray analysis of thyroid hormone binding to prealbumin. Biochem Soc. Trans. 6(6): 1114-1118.
Bloom, M.S., J.E. Vena, J.R. Olson and P.J. Kostyniak. (2009) Assessment of polychlorinated biphenyl congeners, thyroid stimulating hormone, and free thyroxine among New York state anglers. Int. J. Hyg. Environ. Health 212(6): 599-611.
Branchi, I., E. Alleva and L.G. Costa. (2002) Effects of perinatal exposure to a polybrominated diphenyl ether (PBDE 99) on mouse neurobehavioural development. Neurotoxicology 23(3): 375-384.
Brouwer, a, & van den Berg, K. J. (1986). Binding of a metabolite of 3,4,3’,4'-tetrachlorobiphenyl to transthyretin reduces serum vitamin A transport by inhibiting the formation of the protein complex carrying both retinol and thyroxin. Toxicology and Applied Pharmacology, 85(3), 301–312.
Calvo, R.M., E. Jauniaux, B. Gulbis, M. Asuncion, C. Gervy, B. Contempre and G. Morreale de Escobar. (2002) Fetal tissues are exposed to biologically relevant free thyroxine concentrations during early phases of development. J. Clin. Endocrinol. Metab. 87(4); 1768-1777.
Cao, J., L.H. Guo, B. Wan and Y. Wei. (2011) In vitro fluorescence displacement investigation of thyroxine transport disruption by bisphenol A. J. Environ Sci, (China) 23(2): 315-321.
Cao, J., Y. Lin, L.H. Guo, A.Q. Zhang, Y. Wei and Y. Yang. (2010) Structure-based investigation on the binding interaction of hydroxylated polybrominated diphenyl ethers with thyroxine transport proteins. Toxicology 277(1-3): 20-28.
Chan, S.Y., J.A. Franklyn, H.N. Pemberton, J.N. Bulmer, T.J. Visser, C.J. McCabe and M.D. Kilby. (2006) Monocarboxylate transporter 8 expression in the human placenta: the effects of severe intrauterine growth restriction. J. Endocrinol. 189(3): 465-471.
Chan, S., S. Kachilele, C.J. McCabe, L.A. Tannahill, K. Boelaert, N.J. Gittoes, T.J. Visser, J.A. Franklyn and M.D. Kilby. (2002) Early expression of thyroid hormone deiodinases and receptors in human fetal cerebral cortex. Brain Res. Dev. Brain Res. 138(2): 109-116.
Chang, S.C., J.R. Thibodeaux, M.L. Eastvold, D.J. Ehresman, J.A. Bjork, J.W. Froehlich, C. Lau, R.J. Singh, K.B. Wallace and J.L. Butenhoff. (2008) Thyroid hormone status and pituitary function in adult rats given oral doses of perfluorooctanesulfonate (PFOS). Toxicology 243(3): 330-339.
Chanoine, J.-P., Alex, S., Fang, S. L., Stone, S., Leonard, J. L., Kohrle, J., & Braverman, L. E. (1992). Role of transthyretin in the transport of thyroxine from the blood to the choroid plexus, the cerebrospinal fluid and the brain. Endocrinology, 130(2), 933–938.
Chauhan, K. R., Kodavanti, P. R. S., & McKinney, J. D. (2000). Assessing the Role of ortho-Substitution on Polychlorinated Biphenyl Binding to Transthyretin, a Thyroxine Transport Protein. Toxicology and Applied Pharmacology, 162(1), 10–21. http://doi.org/10.1006/taap.1999.8826
Cheek, A.O., K. Kow, J. Chen and J.A. McLachlan. (1999) Potential mechanisms of thyroid disruption in humans: interaction of organochlorine compounds with thyroid receptor, transthyretin, and thyroid-binding globulin. Environ. Health Perspect. 107(4): 273-278.
Chevrier, J., K.G. Harley, A. Bradman, M. Gharbi, A. Sjodin and B. Eskenazi. (2010) Polybrominated diphenyl ether (PBDE) flame retardants and thyroid hormone during pregnancy. Environ. Health Perspect. 118(10) : 1444-1449.
Chopra, I.J., P. Taing and L. Mikus. (1996) Direct determination of free triiodothyronine (T3) in undiluted serum by equilibrium dialysis/radioimmunoassay (RIA). Thyroid 6(4): 255-259.
Costa, L.G., R. de Laat, S. Tagliaferri and C. Pellacani. (2014) A mechanistic view of polybrominated diphenyl ether (PBDE) developmental neurotoxicity. 230(2): 282-294.
Dallaire, R., G. Muckle, E. Dewailly, S.W. Jacobson, J.L. Jacobson, T.M. Sandanger, C.D. Sandau and P. Ayotte. (2009a) Thyroid hormone levels of pregnant inuit women and their infants exposed to environmental contaminants. Environ. Health Perspect. 117(6): 1014-1020.
Dallaire, R., E. Dewailly, D. Pereg, S. Dery and P. Ayotte. (2009b) Thyroid function and plasma concentrations of polyhalogenated compounds in Inuit adults. Environ. Health Perspect. 117(9): 1380-1386.
Darnerud, P.O., D. Morse, E. Klasson-Wehler and A Brouwer. (1996) Binding of a 3,3', 4,4'-tetrachlorobiphenyl (CB-77) metabolite to fetal transthyretin and effects on fetal thyroid hormone levels in mice. Toxicology 106(1-3): 105-114.
De Escobar, G.M., M.J. Obregon and F.E. del Rey. (2004) Maternal thyroid hormones early in pregnancy and fetal brain development. Best Pract. Res. Clin. Endocrinol. Metab. 18(2): 225-248.
Dirinck, E., A.C. Dirtu, G. Malarvanna, A. Covaci, P.G. Jorens and L.F. Van Gall. (2016) A Preliminary Link between Hydroxylated Metabolites of Polychlorinated Biphenyls and Free Thyroxin in Humans. Int. J. Environ. Res. Public Health 13(4): 421.
Eguchi, A., K. Nomiyama, N. Minh Tue, P.T. Trang, P. Hung Viet, S. Takahashi and S. Tanabe. (2015) Residue profiles of organohalogen compounds in human serum from e-waste recycling sites in North Vietnam: Association with thyroid hormone levels. Environ. Res. 137: 440-449.
Emerson, C.H., J.H. Cohen III, R.A Yung, S. Alex and S.L. Fang. (1990) Gender-related differences of serum thyroxine-binding proteins in the rat. Acta Endocrinol. (Copenh) 123(1): 72-78.
Erratico, C.A., A. Steitz and S.M. Bandiera. (2013) Biotransformation of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) by human liver microsomes: identification of cytochrome P450 2B6 as the major enzyme involved. Chem. Res. Toxicol. 26(5): 721-731.
Erratico, C.A., S.C. Moffatt and S.M. Bandiera. (2011) Comparative oxidative metabolism of BDE-47 and BDE-99 by rat hepatic microsomes. Toxicol. Sci. 123(1): 37-47.
Eskenazi, B., J. Chevrier, S.A. Rauch, K. Kogul, K.G. Harley, C. Johnson, C. Trujillo, A. Sjodin and A. Bradman. (2013) In utero and childhood polybrominated diphenyl ether (PBDE) exposures and neurodevelopment in the CHAMACOS study. 121(2) : 257-262.
Feo, M.L., M.S. Gross, B.P. McGarrigle, E. Eljarrat, D. Barcelo, D.S. Aga and J.R. Olson. (2013) Biotransformation of BDE-47 to potentially toxic metabolites is predominantly mediated by human CYP2B6. Environ. Health Persepct. 121(4): 440-446.
Ferguson, R.N., H. Edelhoch, H.A. Saroff, J. Robbins and H.J. Cahnmann (1975) Negative cooperativity in the binding of thyroxine to human serum prealbumin. Preparation of tritium-labeled 8-anilino-1-naphthalenesulfonic acid. Biochemistry 14(2): 282-289.
Friesema EC, Jansen J, Jachtenberg JW, Visser WE, Kester MH, Visser TJ 2008 Effective cellular uptake and efflux of thyroid hormone by human monocarboxylate transporter 10. Molecular endocrinology (Baltimore, Md 22:1357-1369
Friesema EC, Kuiper GG, Jansen J, Visser TJ, Kester MH 2006 Thyroid hormone transport by the human monocarboxylate transporter 8 and its rate-limiting role in intracellular metabolism. Molecular endocrinology (Baltimore, Md 20:2761-2772
Friesma, E.C., J. Jansen and T.J. Visser. (2005) Thyroid hormone transporters. Biochem. Soc. Trans. 33(part 1): 228-232.
Friesema EC, Ganguly S, Abdalla A, Manning Fox JE, Halestrap AP, Visser TJ 2003 Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter. J Biol Chem 278:40128-40135
Grimm, F. a., Lehmler, H. J., He, X., Robertson, L. W., & Duffel, M. W. (2013). Sulfated metabolites of polychlorinated biphenyls are high-affinity ligands for the thyroid hormone transport protein transthyretin. Environmental Health Perspectives, 121(6), 657–662.
Gutshall, D.M., G.D. Pilcher and A.E. Langley. (1989) Mechanism of the serum thyroid hormone lowering effect of perfluoro-n-decanoic acid (PFDA) in rats. J. Toxicol. Environ. Health 28(1): 53-65.
Hagenbuch, B. (2007) Cellular entry of thyroid hormones by organic anion transporting polypeptides. Best Pract. Res. Clin. Endocrinol. Metab. 21(2): 209-221.
Hagenbuch B, Meier PJ 2004 Organic anion transporting polypeptides of the OATP/ SLC21 family: phylogenetic classification as OATP/ SLCO superfamily, new nomenclature and molecular/functional properties. Pflugers Arch 447:653-665
Hagmar, L., L. Rylander, E. Dyremark, E. Klasson-Wehler and E.M. Erfurth. (2001a). Plasma concentrations of persistent organochlorines in relation to thyrotropin and thyroid hormone levels in women. Int. Arch. Occup. Environ. Health 74(3): 184-188.
Hagmar, L., J. Bjork, A. Sjodin, A. Bergman and E.M. Erfurth. (2001b) Plasma levels of persistent organohalogens and hormone levels in adult male humans. Arch. Environ. Health 56(2): 138-143.
Hallgren, S., T. Sinjari, H. Hakansson and P.O. Darnerud. (2001) Effects of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) on thyroid hormone and vitamin A levels in rats and mice. 75(4): 200-208.
Hallgren, S. and P.O. Darnerud. (2002) Polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs) and chlorinated paraffins (CPs) in rats-testing interactions and mechanisms for thyroid hormone effects. Toxicology 177(203): 227-243.
Hamers, T., J.H. Kamstra, E. Sonneveld, A.J. Murk, M.H. Kester, P.L. Andersson, J. Legler and A. Brouwer. (2006) In vitro profiling of the endocrine-disrupting potency of brominated flame retardants. Toxicol. Sci. 92(1): 157-173.
Hamers, T., Kamstra, E. Sonneveld, A.J. Murk, T.J. Visser, M.J. Van Velzen, A. Brouwer and A. Bergman. (2008) Biotransformation of brominated flame retardants into potentially endocrine-disrupting metabolites, with special attention to 2,2',4,4'-tetrabromodiphenyl ether (BDE-47). Mol. Nutr. Food Res. 52(2): 284-298.
Harley, K.G., A.R. Marks, J. Chevrier, A. Bradman, A. Sjodin and B. Eskenazi. (2010) PBDE concentrations in women's serum and fecundability. Environ. Health Perspect. 118(5): 699-704.
Henneman, G., R. Docter, E.C. Friesma, M. de Jong, E.P. Krenning and T.J. Visser. (2001) Plasma membrane transport of thyroid hormones and its role in thyroid hormone metabolism and bioavailability. Endocr. Rev. 22(4): 451-476.
Heuer, H. (2007) The importance of thyroid hormone transporters for brain development and function. Best Pract. Res. Clin. Endocrinol. Metab. 21(2): 265-276.
Hood, A. and C.D. Klaassen. (2000a) Differential effects of microsomal enzyme inducers on in vitro thyroxine (T(4)) and triiodothyronine (T(3)) glucuronidation. Toxicol. Sci. 55(1): 78-84.
Hood, A. and C.D. Klaassen. (2000b) Effects of microsomal enzyme inducers on outer-ring deiodinase activity toward thyroid hormones in various rat tissues. Toxicol. Appl. Pharmacol. 163(3): 240-248.
Hovander, L., M. Athanasiadou, L. Asplund, S. Jensen and E.K. Wehler. (2000). Extraction and cleanup methods for analysis of phenolic and neutral organohalogens in plasma. 24(8): 696-703.
Hume, R., J. Simpson, C. Delahunty, H. van Toor, S.Y. Wu, F.L. Williams, T.J. Visser et al. (2004) Human fetal and cord serum thyroid hormones: developmental trends and interrelationships. J. Clin. Endocrinol. Metab. 89(8): 4097-4103.
Inoue, K., F. Okada, R. Ito, S. Kato, S. Sasaki, S. Nakajima, A. Uno, Y. Saijo, F. Sata, Y. Yoshimura, R. Kishi and H. Nakazawa. (2004) Perfluorooctane sulfonate (PFOS) and related perfluorinated compounds in human maternal and cord blood samples: assessment of PFOS exposure in a susceptible population during pregnancy. Environ. Health Perspect. 112(11): 1204-1207.
Kato, Y., K. Haraguchi, M. Onishi, S. Ikushiro, T. Endo, C. Ohta, N. Koga, S Yamada and M. Degawa. (2014) 3,3',4,4'-Tetrachlorobiphenyl-mediated decrease of serum thyroxine level in C57BL/6 and DBA/2 mice occurs mainly through enhanced accumulation of thyroxine in the liver. Biol. Pharm. Bull. 37(3) 504-509.
Kato, Y., M. Onishi, K. Haraguchi, S. Ikushiro, C. Ohta, N. Koga, T. Endo, S. Yamada and M. Degawa. (2013) A possible mechanism for 2,3',4,4',5'-pentachlorobiphenyl-mediated decrease in serum thyroxine level in mice. Biol. Pharm. Bull. 36(10): 1594-1601.
Kato, Y., S. Tamaki, K. Haraguchi, S. Ikushiro, M. Sekimoto, C. Ohta, T. Endo, N. Koga, S. Yamada and M. Degawa. (2012) Comparative study on 2,2',4,5,5'-pentachlorobiphenyl-mediated decrease in serum thyroxine level between C57BL/6 and its transthyretin-deficient mice. Toxicol. Appl. Pharmacol. 263(3): 323-329.
Kato, Y., M. Onishi, K. Haraguchi, S. Ikushiro, C. Ohta, N. Koga, T. Endo, S. Yamada and M. Degawa. (2011) A possible mechanism for 2,2',4,4',5,5'-hexachlorobiphenyl-mediated decrease in serum thyroxine level in mice. Toxicol. Appl. Pharmacol. 254(1): 48-55.
Kato, Y., K. Haraguchi, M. Kubota, Y. Seto, S. Ikushiro, T. Sakaki, N. Koga, S. Yamada and M. Degawa. (2009) 4-Hydroxy-2,2',3,4',5,5',6-heptachlorobiphenyl-mediated decrease in serum thyroxine level in mice occurs through increase in accumulation of thyroxine in the liver. Drug Metab. Dispos. 37(10): 2095-2102.
Kato, Y., S. Ikushiro, R. Takiguchi, K. Haraguchi, N. Koga, S. Uchida, T. Sakaki, S. Yamada, J. Kanno and M. Degawa. (2007) A novel mechanism for polychlorinated biphenyl-induced decrease in serum thyroxine level in rats. Drug Metab. Dispos. 35(10) : 1949-1955.
Kato, Y., S. Ikushiro, K. Haraguchi, T. Yamazaki, Y. Ito, H. Suzuki, R. Kimura, S. Yamada, T. Inoue and M. Degawa. (2004) A possible mechanism for decrease in serum thyroxine level by polychlorinated biphenyls in Wistar and Gunn rats. Toxicol. Sci. 81(2): 309-315.
Kato, Y., K. Haraguchi, T. Yamazuki, Y. Ito, S. Miyajima, K. Nemoto, N. Koga, R. Kimura and M. Degawa. (2003) Effects of polychlorinated biphenyls, kanechlor-500, on serum thyroid hormone levels in rats and mice. Toxicol. Sci. 72(2): 235-241.
Kim, S.Y., E.S. Choi, H.J. Lee, C. Moon and E. Kim. (2015) Transthyretin as a new transporter of nanoparticles for receptor-mediated transcytosis in rat brain microvessels. Colloids Surf B Biointerfaces 136: 989-996.
Kim do K, Kanai Y, Matsuo H, Kim JY, Chairoungdua A, Kobayashi Y, Enomoto A, Cha SH, Goya T, Endou H 2002 The human T-type amino acid transporter-1: characterization, gene organization, and chromosomal location. Genomics 79:95-103
Kohrle, J., S.L. Fang, Y. Yang, K. Irmscher, R.D. Hesch, S. Pino, S. Alex, and L.E. Braverman. (1989). Rapid effects of the flavonoid EMD 21388 on serum thyroid hormone binding and thyrotropin regulation in the rat. Endocrinoloy 125: 532-537
Koopman-Essenboom, C., D.C. Morse, N. Weisglas-Kuperus, I.J. Lutkeschipholt, C.G. Van der Paauw, L.G. Tuinstra, A. Brouwer and P.J. Sauer. (1994) Effects of dioxins and polychlorinated biphenyls on thyroid hormone status of pregnant women and their infants. Pediatr. Res. 36(4): 468-473.
Lans, M. C., Klasson-Wehler, E., Willemsen, M., Meussen, E., Safe, S., & Brouwer, A. (1993). STRUCTURE-DEPENDENT, COMPETITIVE INTERACTION OF HYDROXY-POLYCHLOROBIPHENYLS, -DIBENZO-p-DIOXINS AND -DIBENZOFURANS WITH HUMAN TRANSTHYRETIN. Chemico-Biological Interactions, 88, 7–21.
Lans, M. C., Spiertz, C., Brouwer, a, & Koeman, J. H. (1994). Different competition of thyroxine binding to transthyretin and thyroxine-binding globulin by hydroxy-PCBs, PCDDs and PCDFs. European Journal of Pharmacology, 270(2-3), 129–136. http://doi.org/10.1016/0926-6917(94)90054-X
Larsson, M., Pettersson, T., & Carlström, a. (1985). Thyroid hormone binding in serum of 15 vertebrate species: isolation of thyroxine-binding globulin and prealbumin analogs. General and Comparative Endocrinology, 58(3), 360–375.
Loubiere, L.S., E. Vasilopoulou, J.N. Bulmer, P.M. Taylor, B. Stieger, F. Verrey, C.J. McCabe, J.A. Franklyn, M.D. Kilby and S.Y. Chan. (2010) Expression of thyroid hormone transporters in the human placenta and changes associated with intrauterine growth restriction. Placenta 31(4): 295-304.
Lueprasitsakul, W., Alex, S., Fang, S. L., Pino, S., Irmscher, K., Köhrle, J., & Braverman, L. E. (1990). Flavonoid administration immediately displaces thyroxine (T4) from serum transthyretin, increases serum free T4, and decreases serum thyrotropin in the rat. Endocrinology 126 (6)
Lupton, S.J., P. McGarrigle, J.R. Olson, T.D. Wood and D.S. Aga. (2010) Analysis of hydroxylated polybrominated diphenyl ether metabolites by liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry. Rapid Commun. Mass. Spectrom. 24(15): 2227-2235.
Lupton, S.J., B.P. McGarrigle, J.R. Olson, T.D. Wood and D.S. Aga. (2009) Analysis of hydroxylated polybrominated diphenyl ether metabolites by liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry. 22(11): 1802-1809.
Malmberg, T., M. Athanasiadou, G. Marsh, I. Brandt and A. Bergman. (2005) Identification of hydroxylated polybrominated diphenyl ether metabolites in blood plasma from polybrominated diphenyl ether exposed rats. 39(14): 5342-5348.
Marchesini, G.R., E. Meulenberg, W. Haasnoot, M. Mizuguchi and H. Irth. (2006) Biosensor recognition of thyroid-disrupting chemicals using transport proteins. Anal. Chem. 78(4): 1107-1114.
Marchesini, G.R., A. Meimaridou, W. Haasnoot, E. Meulenberg, F. Albertus, M. Mizuguchi, M. Takeuchi, H. Irth and A.J. Murk. (2008) iosensor discovery of thyroxine transport disrupting chemicals. Toxicol. Appl. Pharmacol. 232(1): 150-160.
Martin, L.A., D.T. Wilson, K.R> Reuhl, M.A. Gallo and C.D. Klaassen. (2012) Polychlorinated biphenyl congeners that increase the glucuronidation and biliary excretion of thyroxine are distinct from the congeners that enhance the serum disappearance of thyroxine. Drug Metab. Dispos. 40(3): 588-595.
Martin, L. and C.D. Klaassen. (2010) Differential effects of polychlorinated biphenyl congeners on serum thyroid hormone levels in rats. Toxicol. Sci. 117(1): 36-44.
Meerts, I.A., Y. Assink, P.H. Cenjin, J.H. Van Den Berg, B.M. Weijers, A. Bergman, J.H. Koeman and A. Brouwer. (2002) Placental transfer of a hydroxylated polychlorinated biphenyl and effects on fetal and maternal thyroid hormone homeostasis in the rat. Toxicol. Sci. 68(2): 361-371.
Meerts, I.A., J.J. van Zanden, E.A. Lujiks, I. van Leeuwen-Bol, G. Marsh, E. Jakobsson, A. Bergman and A. Brouwer. (2000) Potent competitive interactions of some brominated flame retardants and related compounds with human transthyretin in vitro. Toxicol. Sci. 56(1): 95-104.
Mendel, C. M. (1989). Modeling thyroxine transport to liver : rejection of the “enhanced dissociation” hypothesis as applied to thyroxine. Am J Physiol, 257(Endocrinol Metab 20), E764–E771.
Mendel, C. M., Cavalieri, R. R., & Kohrle, J. (1992). Thyroxine (T4) transport and distribution in rats treated with EMD 21388, a synthetic flavonoid that displaces T4 from transthyretin. Endocrinology, 130(3), 1525–1532.
Midgley, J. E. (2001) Direct and indirect free thyroxine assay methods: theory and practice. Clin. Chem. 47(8): 1353-1363.
Miksys, S. and R.F. Tyndale. (2004) The unique regulation of brain cytochrome P450 2 (CYP2) family enzymes by drugs and genetics. Drug Metab. Rev. 36(2): 313-333.
Montano, M., E. Coccco, C. Guignard, G. Marsh, L. Hoffmann, A. Bergman, A.C. Gutleb and A.J. Murk. (2012) New approaches to assess the transthyretin binding capacity of bioactivated thyroid hormone disruptors. Toxicol. Sci. 130(1): 94-105.
Morse, D.C., E.K. Wehler, W. Wesseling, J.H. Koeman and A. Brouwer. (1996) Alterations in rat brain thyroid hormone status following pre- and postnatal exposure to polychlorinated biphenyls (Aroclor 1254). Toxicol. Appl. Pharmacol. 136(2): 269-279.
Morse, D.C., D. Groen, M. Veerman, C.J. van Amerongen, H.B. Koeter, A.E. Smits van Proojie, T.J. Visser, J.H. Koeman and A. Brouwer. (1993) Interference of polychlorinated biphenyls in hepatic and brain thyroid hormone metabolism in fetal and neonatal rats. Toxicol. Appl. Pharmacol. 122(1) :27-33.
Munro, S.L., C.F. Lim, J.G. Hall, J.W. Barlow, D.J. Craik, D.J. Topliss and J.R. Stockigt (1989) Drug competition for thyroxine binding to transthyretin (prealbumin): comparison with effects on thyroxine-binding globulin. J. Clin. Endocrinol. Metab. 68(6): 1141-1147,
Nishimura M, Naito S 2008 Tissue-specific mRNA expression profiles of human solute carrier transporter superfamilies. Drug Metab Pharmacokinet 23:22-44
Pedraza, P., Calvo, R., Obregón, M. J., Asuncion, M., Escobar Del Rey, F., & Morreale De Escobar, G. (1996). Displacement of T4 from transthyretin by the synthetic flavonoid EMD 21388 results in increased production of T3 from T4 in rat dams and fetuses. Endocrinology, 137(11), 4902–4914. http://doi.org/10.1210/en.137.11.4902
Purkey, H.E., M.I. Dorrell and J.W. Kelly. (2001) Evaluating the binding selectivity of transthyretin amyloid fibril inhibitors in blood plasma. Proc. Natl. Acad. Sci. USA 98(10): 5566-5571.
Refetoff, S., N.I. Robin and V.S. Fang. (1970) Parameters of thyroid function in serum of 16 selected vertebrate species: a study of PBI, serum T4, free T4, and the pattern of T4 and T3 binding to serum proteins. Endocrinology 86(4): 793-805.
Refetoff, S. (2015) Thyroid Hormone Serum Transport Proteins. In: De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000.
Ren, X.M., L.H. Guo, Y. Gao, B.T. Zhang and B. Wan. (2013) Hydroxylated polybrominated diphenyl ethers exhibit different activities on thyroid hormone receptors depending on their degree of bromination. Toxicol. Appl. Pharamacol. 268(3): 256-263.
Ren, X. M., & Guo, L. H. (2012). Assessment of the binding of hydroxylated polybrominated diphenyl ethers to thyroid hormone transport proteins using a site-specific fluorescence probe. Environmental Science and Technology, 46(8), 4633–4640. http://doi.org/10.1021/es2046074
Rerat, C. and H.G. Schwick (1967) [Crystallographic data of blood plasma prealbumin]. [Article in French] Acta Crystallogr. 22(3): 441-442.
Richardson, S. J. (2007). Cell and molecular biology of transthyretin and thyroid hormones. International Review of Cytology, 258(January), 137–93. http://doi.org/10.1016/S0074-7696(07)58003-4
Richardson, S. J., Wijayagunaratne, R. C., D’Souza, D. G., Darras, V. M., & Van Herck, S. L. J. (2015). Transport of thyroid hormones via the choroid plexus into the brain: the roles of transthyretin and thyroid hormone transmembrane transporters. Frontiers in Neuroscience, 9(March), 1–8.
Rickenbacher, U., McKinney, J. D., Oatley, S. J., & Blake, C. C. (1986). Structurally specific binding of halogenated biphenyls to thyroxine transport protein. Journal of Medicinal Chemistry, 29(5), 641–648.
Ritchie, J.W. and P.M. Taylor. (2001) Role of the System L permease LAT1 in amino acid and iodothyronine transport in placenta. Biochem. J. 356(Part 3); 719-725.
Riu, A., J.P. Cravedi, L. Debrauwer, A. Garcia, C. Canlet, I. Jouanin and D. Zalko. (2008) Environ. Int. 34(3): 318-329.
Roberts LM, Woodford K, Zhou M, Black DS, Haggerty JE, Tate EH, Grindstaff KK, Mengesha W, Raman C, Zerangue N 2008 Expression of the thyroid hormone transporters MCT8 (SLC16A2) and OATP14 (SLCO1C1) at the blood-brain barrier. Endocrinology 149:6251-6261
Rotroff, D.M., B.A. Wetmore, D.J. Dix, S.S. Ferguson, H.J. Clewell, K.A. Houck, E.L. Lecluyse, M.E. Anersen, R.S. Judson, C.M. Smith, M.A. Sochaski, R.J. Kavlock, F. Boellmann, M.T. Martin, D.M. Reif, J.F. Wambaugh and R.S. Thomas. (2010) Incorporating human dosimetry and exposure into high-throughput in vitro toxicity screening. 117(2): 348-358.
Sato, K., J. Sugawara, T. Sato, H. Mizutamari, T. Suzuki, A. Ito, T. Mikkaichi, T. Onogawa, M. Tanemoto, M. Unno, T. Abe and K. Okamura. (2003) Expression of organic anion transporting polypeptide E (OATP-E) in human placenta. Placenta 24(2-3): 144-148.
Schreiber, G. (2002). The evolutionary and integrative roles of transthyrein in thyroid hormone homeostasis. Journal of Endocrinology, 175(1), 61–73. http://doi.org/10.1677/joe.0.1750061
Schroder van der Elst, J.P., D. van der Heide, H. Rokos, G. Morreale de Escobar and J. Kohrlre. (1998) Synthetic flavonoids cross the placenta in the rat and are found in fetal brain. Am. J. Physiol. 274(2 Psrt 1): E253-E256.
Schroder van der Elst, J.P., D. van der Heide, H. Rokos, J. Kohrle and G. Morreale de Escobar. (1997) Different tissue distribution, elimination, and kinetics of thyroxine and its conformational analog, the synthetic flavonoid EMD 49209 in the rat. Endocrinology 138(1): 79-84.
Schuur, A.G., F.M. Boekhorst, A. Brouwer and T.J. Visser. (1997) Extrathyroidal effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on thyroid hormone turnover in male Sprague-Dawley rats. Endocrinology 138(9): 3727-3734.
Sinjari, T. and P.O. Darnerud. (1998) Hydroxylated polychlorinated biphenyls: placental transfer and effects on thyroxine in the foetal mouse. Xenobiotica 28(1): 21-30.
Sparkes, R.S., H. Sasaki, T. Mohandas, K. Yoshioka, I. Kilsak, Y. Sasaki, C. Heinzmann and M.I. Simon. (1987) Assignment of the prealbumin (PALB) gene (familial amyloidotic polyneuropathy) to human chromosome region 18q11.2-q12.1. Hum. Genet. 75(2): 151-154.
Stapleton, H.M., S.M. Kelly, R. Pei, R.J. Letcher and C. Gunsch. (2009) Metabolism of polybrominated diphenyl ethers (PBDEs) by human hepatocytes in vitro. Environ. Health Perspect. 117(2): 197-202.
Tohyama K, Kusuhara H, Sugiyama Y 2004 Involvement of multispecific organic anion transporter, Oatp14 (Slc21a14), in the transport of thyroxine across the blood-brain barrier. Endocrinology
Ucan-Marin, F., A. Arukwe, A.S. Mortensen, G.W. Gabrielsen and R.J. Letcher. (2010) Recombinant albumin and transthyretin transport proteins from two gull species and human: chlorinated and brominated contaminant binding and thyroid hormones. Environ. Sci. Technol. 44(1): 497-504.
Van Birgelen, A.P., E.A. Smit, I.M. Kampen, C.N. Groeneveld, K.M. Case, J. Van der Kolk, H. Poiger, M. Van den Berg, J.H. Koeman and A. Brouwer. (1995) Subchronic effects of 2,3,7,8-TCDD or PCBs on thyroid hormone metabolism: use in risk assessment. Eur. J. Pharmacol. 293(1) : 77-85.
Van den Berg, K. J. (1990). Interaction of chlorinated phenols with thyroxine binding sites of human transthyretin, albumin and thyroid binding globulin. Chemico-Biological Interactions, 76(1), 63–75.
Van den Berg, K. J., Van Raaij, J. a G. M., Bragt, P. C., & Notten, W. R. F. (1991). Interactions of halogenated industrial chemicals with transthyretin and effects on thyroid hormone levels in vivo. Archives of Toxicology, 65(1), 15–19.
Viberg, H., A. Fredriksson and P. Eriksson. (2002) Neonatal exposure to the brominated flame retardant 2,2',4,4',5-pentabromodiphenyl ether causes altered susceptibility in the cholinergic transmitter system in the adult mouse. Toxicol. Sci. 67(1): 104-107.
Viollon-Abadie, C., D. Lassere, E. Debruyne, L. Nicod, N. Carmichael and L. Richert. (1999) Phenobarbital, beta-naphthoflavone, clofibrate, and pregnenolone-16alpha-carbonitrile do not affect hepatic thyroid hormone UDP-glucuronosyl transferase activity, and thyroid gland function in mice. Toxicol. Appl. Pharmacol. 155(1) 1-12.
Visser, T.J. and R.P. Peeters. (2012) Metabolism of thyroid hormone. In: De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-.
Visser, T. J. (2010). Cellular Uptake of Thyroid Hormones. In: De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-.
Visser, T.J. (1996) Role of sulfate in thyroid hormone sulfation. Eur. J. Endocrinol. 134(1): 12-14.
Visser, T.J., E. Kaptein, J.A. van Raaij, C.T. Joe, T. Ebner and B. Burchell. (1993)
Multiple UDP-glucuronyltransferases for the glucuronidation of thyroid hormone with preference for 3,3',5'-triiodothyronine (reverse T3). FEBS Lett. 315(1): 65-68.
Weiss, J.M., P.L. Andersson, M.H. Lamoree, P.E. Leonards, S.P. van Leeuwen and T. Hamers. (2009) Competitive binding of poly- and perfluorinated compounds to the thyroid hormone transport protein transthyretin. Toxicol. Sci. 109(2): 206-216.
Weiss, J. M., Andersson, P. L., Zhang, J., Simon, E., Leonards, P. E. G., Hamers, T., & Lamoree, M. H. (2015). Tracing thyroid hormone-disrupting compounds: database compilation and structure-activity evaluation for an effect-directed analysis of sediment. Analytical and Bioanalytical Chemistry, 5625–5634. http://doi.org/10.1007/s00216-015-8736-9
Yamauchi, K., A. Ishihara, H. Fukazawa and Y. Terao. (2003) Competitive interactions of chlorinated phenol compounds with 3,3',5-triiodothyronine binding to transthyretin: detection of possible thyroid-disrupting chemicals in environmental waste water. Toxicol. Appl. Pharmacol. 187(2): 110-117.
Yen, P. M. (2001). Physiological and molecular basis of thyroid hormone action. Physiological Reviews, 81(3), 1097–1142.
Zhang, J., J.H. Kamstra, M. Ghorbanzadeh, J.M. Weiss, T. Hamers and P.L. Andersson. (2015) In Silico Approach To Identify Potential Thyroid Hormone Disruptors among Currently Known Dust Contaminants and Their Metabolites. Environ. Sci. Technol. 49(16): 10099-10107.
Zoeller, R. T., Tan, S. W., & Tyl, R. W. (2007). General background on the hypothalamic-pituitary-thyroid (HPT) axis. Critical Reviews in Toxicology, 37(1-2), 11–53.
Zoeller, R.T. and J. Rovet. (2004) Timing of thyroid hormone action in the developing brain: clinical observations and experimental findings. J. Neuroendocrinol. 16(10): 809-818.