Intracellular thyroid hormone metabolism as a local regulator of nuclear thyroid hormone receptor-mediated impact on vertebrate development

Darras, Veerle; Houbrechts, Anne; Herck, Stijn L.J. Van

doi:10.1016/j.bbagrm.2014.05.004

Cited by 68 publications

(62 citation statements)

References 133 publications

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“…For genomic actions of THs within the cell nucleus, T4 can be deiodinated to T3 (considered the “active” form of TH). The family of deiodinases can either activate (e.g., T4 to T3) or inactivate (e.g., T3 to T2; T4 to rT3) THs within the cell (Darras et al, 2015). T3 exerts genomic effects by binding to TRs which are nuclear transcription factors.…”

Section: Thyroid Hormonesmentioning

confidence: 99%

“…Possibly, this could be due to different combinations of TH transmembrane transporters in the choroid plexus and at the blood-brain barrier, thereby partially compensating for the lack of choroid plexus-derived TTR in mice (but equivalent mechanisms lacking in humans). For example, Lat2 is synthesized in the choroid plexus of mice but not in the choroid plexus of humans (Wirth et al, 2009) or chickens (Darras et al, 2015). This may be an explanation for the mild phenotype of TTR null mice, yet the apparent absence of humans lacking TTR.…”

Section: Th Transmembrane Transportersmentioning

confidence: 99%

“…A recent, comprehensive review on expression of TH transmembrane transporters during development in zebrafish, Xenopus tropicalis , chicken, and mouse (Darras et al, 2015) highlights how much is still unknown. Whilst the developing choroid plexus has only been analyzed for TH transmembrane transporters in a few species, interesting differences are emerging.…”

Section: Th Transmembrane Transportersmentioning

confidence: 99%

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Transport of thyroid hormones via the choroid plexus into the brain: the roles of transthyretin and thyroid hormone transmembrane transporters

et al. 2015

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Thyroid hormones are key players in regulating brain development. Thus, transfer of appropriate quantities of thyroid hormones from the blood into the brain at specific stages of development is critical. The choroid plexus forms the blood-cerebrospinal fluid barrier. In reptiles, birds and mammals, the main protein synthesized and secreted by the choroid plexus is a thyroid hormone distributor protein: transthyretin. This transthyretin is secreted into the cerebrospinal fluid and moves thyroid hormones from the blood into the cerebrospinal fluid. Maximal transthyretin synthesis in the choroid plexus occurs just prior to the period of rapid brain growth, suggesting that choroid plexus-derived transthyretin moves thyroid hormones from blood into cerebrospinal fluid just prior to when thyroid hormones are required for rapid brain growth. The structure of transthyretin has been highly conserved, implying strong selection pressure and an important function. In mammals, transthyretin binds T4 (precursor form of thyroid hormone) with higher affinity than T3 (active form of thyroid hormone). In all other vertebrates, transthyretin binds T3 with higher affinity than T4. As mammals are the exception, we should not base our thinking about the role of transthyretin in the choroid plexus solely on mammalian data. Thyroid hormone transmembrane transporters are involved in moving thyroid hormones into and out of cells and have been identified in many tissues, including the choroid plexus. Thyroid hormones enter the choroid plexus via thyroid hormone transmembrane transporters and leave the choroid plexus to enter the cerebrospinal fluid via either thyroid hormone transmembrane transporters or via choroid plexus-derived transthyretin secreted into the cerebrospinal fluid. The quantitative contribution of each route during development remains to be elucidated. This is part of a review series on ontogeny and phylogeny of brain barrier mechanisms.

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Section: Thyroid Hormonesmentioning

confidence: 99%

Section: Th Transmembrane Transportersmentioning

confidence: 99%

Section: Th Transmembrane Transportersmentioning

confidence: 99%

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Transport of thyroid hormones via the choroid plexus into the brain: the roles of transthyretin and thyroid hormone transmembrane transporters

et al. 2015

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“…Thus, malformations of the eyes and retinal cells might ultimately translate in a reduction of their individual fitness. The eye and craniofacial development of vertebrates is a complex process that is partially regulated by thyroid hormones (Bohnsack and Kahana, 2013;Darras et al, 2015). Knock-down of specific thyroid-regulating genes as well as treatment with different thyroid disruptors resulted in reduced eye size, malformations of eyes and head, and disruption of retinal pigment cell layers of zebrafish larvae (Heijlen et al, 2014;Reider and Connaughton, 2014).…”

Section: Introductionmentioning

confidence: 99%

Thyroid disruption in zebrafish (Danio rerio) larvae: Different molecular response patterns lead to impaired eye development and visual functions

et al. 2016

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The vertebrate thyroid system is important for multiple developmental processes, including eye development. Thus, its environmentally induced disruption may impact important fitnessrelated parameters like visual capacities and behaviour. The present study investigated the relation between molecular effects of thyroid disruption and morphological and physiological changes of eye development in zebrafish (Danio rerio). Two test compounds representing different molecular modes of thyroid disruption were used: propylthiouracil (PTU), which is an enzyme-inhibitor of thyroid hormone synthesis, and tetrabromobisphenol A (TBBPA), which interacts with the thyroid hormone receptors. Both chemicals significantly altered transcript levels of thyroid system-related genes (TR, TR, TPO, TSH, DIO1, DIO2 and DIO3) in a compound-specific way. Despite these different molecular response patterns, both treatments resulted in similar pathological alterations of the eyes such as reduced size, RPE cell diameter and pigmentation, which were concentration-dependent. The morphological changes translated into impaired visual performance of the larvae: the optokinetic response was significantly and concentrationdependently decreased in both treatments, together with a significant increase of light preference of PTU-treated larvae. In addition, swimming activity was impacted. This study provides first evidence that different modes of molecular action of the thyroid disruptors can be associated with uniform apical responses. Furthermore, this study is the first to show that pathological eye development, as it can be induced by exposure to thyroid disruptors, indeed translates into impaired visual capacities of zebrafish early life stages. Abstract:The vertebrate thyroid system is important for multiple developmental processes, including eye development. Thus, its environmentally induced disruption may impact important fitnessrelated parameters like visual capacities and behaviour. The present study investigated the relation between molecular effects of thyroid disruption and morphological and physiological changes of eye development in zebrafish (Danio rerio). Two test compounds representing different molecular modes of thyroid disruption were used: propylthiouracil (PTU), which is an enzyme-inhibitor of thyroid hormone synthesis, and tetrabromobisphenol A (TBBPA), which interacts with the thyroid hormone receptors. Both chemicals significantly altered transcript levels of thyroid system-related genes (TR, TR, TPO, TSH, DIO1, DIO2 and DIO3) in a compound-specific way. Despite these different molecular response patterns, both treatments resulted in similar pathological alterations of the eyes such as reduced size, RPE cell diameter and pigmentation, which were concentration-dependent. The morphological changes translated into impaired visual performance of the larvae: the optokinetic response was significantly and concentration-dependently decreased in both treatments, together with a significant increase of light preference of PT...

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“…A tight correspondence exists between measurable deiodinase activity and the status of dio2 and dio3 mRNA Becker et al, 1997;Darras et al, 2015;Galton, 1988;Hiebert, 1987, 1988). Dio2 and dio3 mRNA expression patterns reported herein were consistent with previous observations of enzyme activity in premetamorphic tadpoles (Becker et al, 1997;Galton, 1988;Galton and Hiebert, 1988).…”

Section: Discussionmentioning

confidence: 94%

Rethinking the biological relationships of the thyroid hormones, l-thyroxine and 3,5,3′-triiodothyronine

Maher

Wojnarowicz

Ichu

et al. 2016

Comparative Biochemistry and Physiology Part D: Genomics and Pr

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Intracellular thyroid hormone metabolism as a local regulator of nuclear thyroid hormone receptor-mediated impact on vertebrate development

Cited by 68 publications

References 133 publications

Transport of thyroid hormones via the choroid plexus into the brain: the roles of transthyretin and thyroid hormone transmembrane transporters

Transport of thyroid hormones via the choroid plexus into the brain: the roles of transthyretin and thyroid hormone transmembrane transporters

Thyroid disruption in zebrafish (Danio rerio) larvae: Different molecular response patterns lead to impaired eye development and visual functions

Rethinking the biological relationships of the thyroid hormones, l-thyroxine and 3,5,3′-triiodothyronine

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