Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2008) 16 P708

1Institute for Experimental Endocrinology, Charité-Universitätsmedizin Berlin, Berlin, Germany; 2Institute for Experimental Pediatric Endocrinology, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Thyroid hormones are essential for the proper development of a variety of tissues, especially the nervous system. Their transport into target cells is mediated by specific thyroid hormone transporters like the monocarboxylate transporter 8 (MCT8). Mutations in this X-chromosomal gene in humans lead to a severe phenotype characterized by psychomotor retardation, hypotonia, and a striking derangement of serum thyroid hormone levels: high T3 in the presence of low T4, and no significant changes in TSH. Interestingly, despite high serum T3 the patients do not show tachycardia. Here, we present data on the expression of MCT8 in various human and mouse tissues, as well as on clinical phenotypes of MCT8 knock-out mice. To this end, we submitted MCT8-deficient mice to a comprehensive phenotypical screen at the German Mouse Clinic, located at the GSF in Munich. MCT8-deficient mice replicated the hormonal phenotype of the patients, but did not exhibit neurological deficits and hypotonia. No obvious neuroanatomical changes were observed in MCT8 knock-out mice as analyzed by immunohistochemistry. Nevertheless, the loss of the transporter causes behavioral changes that need further investigation. T3 transport is significantly impaired in MCT8-deficient primary cortical neurons. Systematic analysis of candidate thyroid hormone transporters in primary cortical neurons identified several other transporters that may be involved in compensation of the neurological phenotype almost absent in mice. Since some organs show either a hypothyroid, normal, or hyperthyroid phenotype, we speculate that every organ and tissue may be equipped with different thyroid hormone transporters and their differential response may depend on whether MCT8 is limiting T3 transport or not.

Supported by grants of the DFG.

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