Retinoic Acid Induces Expression of the Thyroid Hormone Transporter, Monocarboxylate Transporter 8 (Mct8)

Kogai, Takahiko; Liu, Yanyun; Richter, Laura L.; Mody, Kaizeen; Kagechika, Hiroyuki; Brent, Gregory A.

doi:10.1074/jbc.m110.123158

Cited by 30 publications

(23 citation statements)

References 52 publications

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“…The effect of MCT8 on gene transcriptional regulation was previously investigated in fibroblasts derived from AHDS patients (54); however, very little is known about the transcriptional regulation of the mct8 gene. An in vitro study performed on mouse cells revealed the presence of a putative mct8 core promoter containing an SP1 binding site that might be important for mct8 transcriptional regulation (55). Here, we isolated, for the first time, a mct8 promoter that contains distinct regulatory regions and that is functional in vivo.…”

Section: Discussionmentioning

confidence: 97%

Zebrafish as a Model for Monocarboxyl Transporter 8-Deficiency

Vatine

Zada

Lerer-Goldshtein

et al. 2013

Journal of Biological Chemistry

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Background: Mutations in the thyroid hormone transporter MCT8 are associated with the psychomotor retardation Allan-Herndon-Dudley syndrome (AHDS). Results: In zebrafish, as in humans, mct8 is expressed primarily in the nervous system. Elimination of MCT8 causes severe neural impairment. Conclusion: MCT8 is a crucial regulator during zebrafish embryonic development. Significance: Establishment of the first vertebrate model for MCT8 deficiency, which exhibits a neurological phenotype.

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Section: Discussionmentioning

confidence: 97%

Zebrafish as a Model for Monocarboxyl Transporter 8-Deficiency

Vatine

Zada

Lerer-Goldshtein

et al. 2013

Journal of Biological Chemistry

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“…Mct8 expression by retinoic acid (21), although the effect on Mct8 expression in the thyroid remains unknown. Given its recently discovered role in mediating TH secretion from the thyroid gland (15,17), we investigated a role for PBF in MCT8 regulation.…”

Section: Studies Of the Mouse Mct8 Gene Have Demonstrated Cell-specifmentioning

confidence: 98%

PTTG-Binding Factor (PBF) Is a Novel Regulator of the Thyroid Hormone Transporter MCT8

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Turnell

Sharma³

et al. 2012

Endocrinology

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Within the basolateral membrane of thyroid follicular epithelial cells, two transporter proteins are central to thyroid hormone (TH) biosynthesis and secretion. The sodium iodide symporter (NIS) delivers iodide from the bloodstream into the thyroid, and after TH biosynthesis, monocarboxylate transporter 8 (MCT8) mediates TH secretion from the thyroid gland. Pituitary tumor-transforming gene-binding factor (PBF; PTTG1IP) is a protooncogene that is up-regulated in thyroid cancer and that binds NIS and modulates its subcellular localization and function. We now show that PBF binds MCT8 in vitro, eliciting a marked shift in MCT8 subcellular localization and resulting in a significant reduction in the amount of MCT8 at the plasma membrane as determined by cell surface biotinylation assays. Colocalization and interaction between PBF and Mct8 was also observed in vivo in a mouse model of thyroid-specific PBF overexpression driven by a bovine thyroglobulin (Tg) promoter (PBF-Tg). Thyroidal Mct8 mRNA and protein expression levels were similar to wild-type mice. Critically, however, PBF-Tg mice demonstrated significantly enhanced thyroidal TH accumulation and reduced TH secretion upon TSH stimulation. Importantly, Mct8-knockout mice share this phenotype. These data show that PBF binds and alters the subcellular localization of MCT8 in vitro, with PBF overexpression leading to an accumulation of TH within the thyroid in vivo. Overall, these studies identify PBF as the first protein to interact with the critical TH transporter MCT8 and modulate its function in vivo. Furthermore, alongside NIS repression, PBF may thus represent a new regulator of TH biosynthesis and secretion.

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“…The timing of the transport of thyroid hormone is tied to RA based on the stimulation of MCT8 gene expression. Using a neuronal cell model, RA was shown to stimulate MCT8 mRNA expression and to confer thyroid hormone transport (103).…”

Section: Tr Isoforms and Neural Developmentmentioning

confidence: 99%

Mechanisms of thyroid hormone action

Brent¹

2012

J. Clin. Invest.

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883

632

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Our understanding of thyroid hormone action has been substantially altered by recent clinical observations of thyroid signaling defects in syndromes of hormone resistance and in a broad range of conditions, including profound mental retardation, obesity, metabolic disorders, and a number of cancers. The mechanism of thyroid hormone action has been informed by these clinical observations as well as by animal models and has influenced the way we view the role of local ligand availability; tissue and cell-specific thyroid hormone transporters, corepressors, and coactivators; thyroid hormone receptor (TR) isoform-specific action; and cross-talk in metabolic regulation and neural development. In some cases, our new understanding has already been translated into therapeutic strategies, especially for treating hyperlipidemia and obesity, and other drugs are in development to treat cardiac disease and cancer and to improve cognitive function.

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Retinoic Acid Induces Expression of the Thyroid Hormone Transporter, Monocarboxylate Transporter 8 (Mct8)

Cited by 30 publications

References 52 publications

Zebrafish as a Model for Monocarboxyl Transporter 8-Deficiency

Zebrafish as a Model for Monocarboxyl Transporter 8-Deficiency

PTTG-Binding Factor (PBF) Is a Novel Regulator of the Thyroid Hormone Transporter MCT8

Mechanisms of thyroid hormone action

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