Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2009) 19 P201

SFEBES2009 Poster Presentations Growth and development (15 abstracts)

Monocarboxylate transporter 8 (MCT8) in human fetal central nervous system (CNS) development

S-Y Chan 1,2 , A Martin-Santos 1 , LS Loubiere 1 , AM Gonzalez 1 , P Cox 2 , A Logan 1 , CJ McCabe 1 , JA Franklyn 1 & MD Kilby 1,2

1University of Birmingham, Birmingham, West Midland, UK; 2Birmingham Women’s Hospital, Birmingham, West Midland, UK.

Mutations in the plasma membrane thyroid hormone (TH) transporter, MCT8, are associated with severe global neurological deficits accompanied by abnormal circulating TH levels. We have previously shown that MCT8 over-expression in human neuronal precursor cells (NT2) increases cellular T3 uptake and reduces proliferation.

Objectives: To quantify and localise the expression of MCT8 in human fetal CNS and to investigate the role of MCT8 in NT2 neurodifferentiation.

Methods and results: (A) Studies in the human fetal cerebral cortex: With ethical approval (1) MCT8 mRNA expression assessed by quantitative RT-PCR (QPCR) remained unchanged in fetal cortical biopsies (n=65) from 6–20 weeks gestation (weeks) compared to adult samples (n=10); (2) MCT8 protein was localised by immunohistochemistry to neurons in the cortical plate, migratory neurons in the subplate zone, the epithelium of the choroid plexus and ependyma, and to the capillary endothelium. (B) Comparing retinoic acid (RA) induced neurodifferentiation of NT2 cells over 21 days in T3-depleted with T3-replete media: (1) endogenous MCT8 mRNA expression was 2-fold higher on day 7 of RA treatment with T3-depletion compared with T3-repletion (P<0.01); (2) nestin mRNA expression was 2-fold greater on day 3 with T3-repletion compared to T3-depletion (P<0.05) but no differences were seen in pou5F1, neuroD1 and synaptophysin mRNA expression by QPCR; (3) there was no significant difference in primary neurite length or neuronal branching in neurons differentiated in either media.

Conclusions: MCT8 is likely to play a crucial role in the uptake of TH into the human fetal CNS through the blood brain barrier and from the cerebrospinal fluid, and also into developing neurons from very early gestation. The up-regulation of MCT8 during early neurodifferentiation in a T3-depleted environment may compensate for the lack of intracellular T3 and thus attenuate the adverse effects of T3 deficiency upon neurodifferentiation and neuronal morphology.

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