New insights on thyroid hormone and the brain

Bernal, Juan

doi:10.1016/j.coemr.2017.12.001

Cited by 6 publications

(3 citation statements)

References 38 publications

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“…The disconnect between altered TH signaling in the fetal brain, neurodevelopmental consequences, and serum TH has been demonstrated using several gene knock-out (KO) mouse models with deficiencies in genes encoding DIO enzymes, TRs, monocarboxylate transporter (MCT)8, organic anion transporter polypeptide (OATP)1c1, and other TH transporters (as reviewed by Bárez-López et al. 2018; Bernal 2018; Hernandez et al. 2010; Richard and Flamant 2018).…”

Section: Discussionmentioning

confidence: 99%

“…Although there is qualitative evidence linking the MIEs listed in Table 2 to altered serum TH, data to establish quantitative KE relationships helpful for regulatory application are lacking. Furthermore, the large diversity of genes regulated directly and indirectly by T3, the nongenomic effects of T4, and our limited knowledge of the functioning of TH during fetal development present a challenge for predicting chemical-induced adverse outcomes from in vitro data (as reviewed by Bernal 2018; Richard and Flamant 2018).…”

Section: Discussionmentioning

confidence: 99%

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Evaluating Chemicals for Thyroid Disruption: Opportunities and Challenges with in Vitro Testing and Adverse Outcome Pathway Approaches

Noyes

Friedman

Browne

et al. 2019

Environ Health Perspect

130

136

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Background:Extensive clinical and experimental research documents the potential for chemical disruption of thyroid hormone (TH) signaling through multiple molecular targets. Perturbation of TH signaling can lead to abnormal brain development, cognitive impairments, and other adverse outcomes in humans and wildlife. To increase chemical safety screening efficiency and reduce vertebrate animal testing, in vitro assays that identify chemical interactions with molecular targets of the thyroid system have been developed and implemented.Objectives:We present an adverse outcome pathway (AOP) network to link data derived from in vitro assays that measure chemical interactions with thyroid molecular targets to downstream events and adverse outcomes traditionally derived from in vivo testing. We examine the role of new in vitro technologies, in the context of the AOP network, in facilitating consideration of several important regulatory and biological challenges in characterizing chemicals that exert effects through a thyroid mechanism.Discussion:There is a substantial body of knowledge describing chemical effects on molecular and physiological regulation of TH signaling and associated adverse outcomes. Until recently, few alternative nonanimal assays were available to interrogate chemical effects on TH signaling. With the development of these new tools, screening large libraries of chemicals for interactions with molecular targets of the thyroid is now possible. Measuring early chemical interactions with targets in the thyroid pathway provides a means of linking adverse outcomes, which may be influenced by many biological processes, to a thyroid mechanism. However, the use of in vitro assays beyond chemical screening is complicated by continuing limits in our knowledge of TH signaling in important life stages and tissues, such as during fetal brain development. Nonetheless, the thyroid AOP network provides an ideal tool for defining causal linkages of a chemical exerting thyroid-dependent effects and identifying research needs to quantify these effects in support of regulatory decision making. https://doi.org/10.1289/EHP5297

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Evaluating Chemicals for Thyroid Disruption: Opportunities and Challenges with in Vitro Testing and Adverse Outcome Pathway Approaches

Noyes

Friedman

Browne

et al. 2019

Environ Health Perspect

130

136

View full text Add to dashboard Cite

show abstract

“…Interestingly, among several membrane transporters with thyroid hormone transporting capacity are OATPs [51], the family of solute carrier transporters that EcI belongs to [2]. Moreover, it has been shown that these thyroid hormone transporters, including OATPs, are expressed in the BBB and play critical roles in thyroid hormone incorporation into the brain [52][53][54], lack of which leads to neurological disorders [55][56][57][58]. It would therefore be important to investigate functions of OATPs in controlling permeability of lipophilic hormones, including steroid hormones, across the BBB in mammals.…”

Section: Regulation Of Lipophilic Hormone Permeability Across the Bbb By Organic Anion Transporting Polypeptidesmentioning

confidence: 99%