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THE THYROID HORMONE TRANSPORTER, MCT8, SELECTIVELY RESPONDS TO THYROID HORMONE INSUFFICIENCY IN THE DEVELOPMENT RAT BRAIN.
SHARLIN, D. S., D. TIGHE, R. BANSAL, M. E. GILBERT, AND T. ZOELLER. THE THYROID HORMONE TRANSPORTER, MCT8, SELECTIVELY RESPONDS TO THYROID HORMONE INSUFFICIENCY IN THE DEVELOPMENT RAT BRAIN. Presented at Society of Toxicology, Charlotte, NC, March 25 - 29, 2007.
Therefore, the aim of this study was to test the hypothesis that the neuronal T3 transporter, MCT8, responds to TH insufficiency in a brain region-specific manner.
Thyroid hormone (TH) is essential for normal brain development. Therefore, it is not surprising that a variety of adaptive mechanisms are activated in response to TH insufficiency. However, not all brain regions respond in the same fashion to TH insufficiency. This observation suggests that different brain regions may have different capabilities to adapt to insufficient TH during development. One mechanism that may account for the differential ability of a particular brain region to adapt to TH insufficiency is that the cells contained in these regions have an independent capacity to uptake TH. Recently, a cell membrane bound transporter that facilitates the cellular uptake of triiodothyronine (T3), monocarboxylate transporter 8 (MCT8), has been characterized and localized to populations of TH-sensitive neurons. Considering the role of MCT8 in cellular uptake of T3, it is possible that MCT8 is an adaptive mechanism that responds to low TH. Therefore, the aim of this study was to test the hypothesis that the neuronal T3 transporter, MCT8, responds to TH insufficiency in a brain region-specific manner. To test this, we determined whether the abundance of MCT8 mRNA was altered in the hippocampus and retrosplenial granular cortex (RSG) using in situ hybridization in postnatal day 15 rat pups following either severe or moderate developmental TH insufficiency. These animals exhibited graded TH insufficiency ranging from 34 % reduction in total serum T4 (moderate) to undetectable levels (severe). To test whether changes in MCT8 expression are associated with compensation (i.e. maintenance of TH-regulated gene expression during perturbations in TH levels), we evaluated the effects of thyroidal status on the expression of the TH-responsive gene, RC3. In addition, we also measured D2 expression, as it is also known to be regulated by thyroidal state. We found that MCT8 expression was significantly increased in the CA1/3 subfields hippocampus and ventral RSG, but not in the dentate gyrus or dorsal RSG. Moreover, we observed that this increase correlated with the severity of TH insufficiency. The greatest decrease in RC3 expression was observed in brain regions in which MCT8 expression did not respond to low TH. Considering these results, MCT8 may represent an important site-specific adaptive mechanism that selectively protects some brain regions, and some cells, from the adverse effects of low TH during development. (Does not reflect US EPA policy.)
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
NEUROPHYSIOLOGICAL TOXICOLOGY BRANCH