Thyroid Hormone Transporters

Thyroid hormone is essential for the development of the brain and the nervous system. Cellular entry is required for conversion of thyroid hormones by the intracellular deiodinases and for binding of T3 to its nuclear receptors. Several transporters capable of thyroid hormone transport have been identified. Functional expression studies using Xenopus laevis oocytes have so far identified two categories of transporters involved in thyroid hormone uptake (i.e., organic anion transporters and amino acid transporters). Among the organic anion transporters, both Na+{plus 45 degree rule}taurocholate cotransporting polypeptide (NTCP) and various members of the organic anion transporting polypeptide (OATP) family mediate transport of iodothyronines. Because iodothyronines are a particular class of amino acids derived from tyrosine residues, it is no surprise that some amino acid transporters have been shown to be involved in thyroid hormone transport. We have characterized monocarboxylate transporter 8 (MCT8) as a very active and specific thyroid hormone transporter, the gene of which is located on the X chromosome. MCT8 is highly expressed in liver and brain but is also widely distributed in other tissues. MCT8 shows 50% amino acid identity with a system T amino acid transporter 1 (TAT1). TAT1, also called MCT10, has been characterized to transport aromatic amino acids but no iodothyronines. We have also found that mutations in MCT8 are associated with severe X-linked psychomotor retardation and strongly elevated serum T3 levels in young boys

Operator exposure to x-ray in left and right radial access during percutaneous coronary procedures: OPERA randomised study

Objective Left radial access (LRA) and right radial access (RRA) have been shown to be safe and effective for coronary arteries catheterisation. However, the differences between the two approaches in terms of radiation exposure are still unclear. The aim of the present investigation is to evaluate in a randomised study, the dose of radiation absorbed by operators using either LRA or RRA. Design Randomised, prospective, double arm, single centre study. Setting University Hospital. Patients Male or female subjects with stable, unstable angina and silent ischaemia. Interventions The present study is a comparison of LRA and RRA for coronary artery catheterisation in terms of operators' radiation exposure. Main outcome measures The primary outcome measure was the radiation dose absorbed by operators; secondary outcome measures were fluoroscopy time, dose-area product and contrast delivered. Results A total of 413 patients were enrolled; 209 were randomly selected to undergo diagnostic procedures with RRA and 204 with LRA. The operator's radiation exposure was significantly lower in the left radial group (LRA 33±37 μSv vs RRA 44±32 μSv, p=0.04). No significant differences were observed in fluoroscopy time (LRA 349±231s vs RRA 370±246 s p=0.09) and dose-area product (LRA 7011.42 ±3617.30 μGym2 vs RRA 7382.38±5226.61 μGym2, p=0.80), even though in both there was a trend towards a lower level in the LRA. No differences were observed in contrast medium delivered (LRA 89.92±32.55 ml vs RRA 88.88±35.35 ml, p=0.45). Conclusions The LRA was associated in the present report with a lower radiation dose absorbed by the operator during coronary angiography

Functional analysis of monocarboxylate transporter 8 mutations identified in patients with X-linked psychomotor retardation and elevated serum triiodothyronine

Context: T-3 action in neurons is essential for brain development. Recent evidence indicates that monocarboxylate transporter 8 (MCT8) is important for neuronal T-3 uptake. Hemizygous mutations have been identified in the X-linked MCT8 gene in boys with severe psychomotor retardation and elevated serum T-3 levels. Objective: The objective of this study was to determine the functional consequences of MCT8 mutations regarding transport of T-3. Design: MCT8 function was studied in wild-type or mutant MCT8-transfected JEG3 cells by analyzing: 1) T-3 uptake, 2) T-3 metabolism in cells cotransfected with human type 3 deiodinase, 3) immunoblotting, and 4) immunocytochemistry. Results: The mutations identified in MCT8 comprise four deletions (24.5 kb, 2.4 kb, 14 bp, and 3 bp), three missense mutations (Ala224Val, Arg271His, and Leu471Pro), a nonsense mutation (Arg245stop), and a splice site mutation (94 amino acid deletion). All tested mutants were inactive in uptake and metabolism assays, except MCT8 Arg271His, which showed approximately 20% activity vs. wild-type MCT8. Conclusion: These findings support the hypothesis that the severe psychomotor retardation and elevated serum T-3 levels in these patients are caused by inactivation of the MCT8 transporter, preventing action and metabolism of T-3 in central neurons