The expression of thyroid hormone transporters in the human fetal cerebral cortex during early development and in N‐Tera‐2 neurodifferentiation
- 1 June 2011
- journal article
- Published by Wiley in The Journal of Physiology
- Vol. 589 (11), 2827-2845
- https://doi.org/10.1113/jphysiol.2011.207290
Abstract
Associations of neurological impairment with mutations in the thyroid hormone (TH) transporter, MCT8, and with maternal hypothyroxinaemia, suggest that THs are crucial for human fetal brain development. It has been postulated that TH transporters regulate the cellular supply of THs within the fetal brain during development. This study describes the expression of TH transporters in the human fetal cerebral cortex (7–20 weeks gestation) and during retinoic acid induced neurodifferentiation of the human N-Tera-2 (NT2) cell line, in triiodothyronine (T3) replete and T3-depleted media. Compared with adult cortex, mRNAs encoding OATP1A2, OATP1C1, OATP3A1 variant 2, OATP4A1, LAT2 and CD98 were reduced in fetal cortex at different gestational ages, whilst mRNAs encoding MCT8, MCT10, OATP3A1 variant 1 and LAT1 were similar. From the early first trimester, immunohistochemistry localised MCT8 and MCT10 to the microvasculature and to undifferentiated CNS cells. With neurodifferentiation, NT2 cells demonstrated declining T3 uptake, accompanied by reduced expressions of MCT8, LAT1, CD98 and OATP4A1. T3 depletion significantly reduced MCT10 and LAT2 mRNA expression at specific time points during neurodifferentiation but there were no effects upon T3 uptake, neurodifferentiation marker expression or neurite lengths and branching. MCT8 repression also did not affect NT2 neurodifferentiation. In conclusion, many TH transporters are expressed in the human fetal cerebral cortex from the first trimester, which could regulate cellular TH supply during early development. However, human NT2 neurodifferentiation is not dependent upon T3 or MCT8 and there were no compensatory changes to promote T3 uptake in a T3-depleted environment.This publication has 77 references indexed in Scilit:
- Differential Triiodothyronine Responsiveness and Transport by Human Cytotrophoblasts from Normal and Growth-Restricted PregnanciesJournal of Clinical Endocrinology & Metabolism, 2010
- Essential Molecular Determinants for Thyroid Hormone Transport and First Structural Implications for Monocarboxylate Transporter 8*Journal of Biological Chemistry, 2010
- Retinoic Acid Induces Expression of the Thyroid Hormone Transporter, Monocarboxylate Transporter 8 (Mct8)Published by Elsevier BV ,2010
- Thyroid Hormone-Regulated Mouse Cerebral Cortex Genes Are Differentially Dependent on the Source of the Hormone: A Study in Monocarboxylate Transporter-8-and Deiodinase-2-Deficient MiceEndocrinology, 2010
- Evidence for a Homodimeric Structure of Human Monocarboxylate Transporter 8Endocrinology, 2009
- Importance of Monocarboxylate Transporter 8 for the Blood-Brain Barrier-Dependent Availability of 3,5,3′-Triiodo-l-ThyronineEndocrinology, 2009
- Changes in the central component of the hypothalamus-pituitary-thyroid axis in a rabbit model of prolonged critical illnessCritical Care, 2009
- Overexpression of MCT8 enhances the differentiation of ES cells into neural progenitorsBiochemical and Biophysical Research Communications, 2007
- Abnormal thyroid hormone metabolism in mice lacking the monocarboxylate transporter 8JCI Insight, 2007
- Monocarboxylate transporter 8 expression in the human placenta: the effects of severe intrauterine growth restrictionJournal of Endocrinology, 2006