Consequences of monocarboxylate transporter 8 deficiency for renal transport and metabolism of thyroid hormones in mice

Marija Trajkovic-Arsic, Theo J Visser, Veerle M Darras, Edith C H Friesema, Bernhard Schlott, Jens Mittag, Karl Bauer, Heike Heuer


Patients carrying inactivating mutations in the gene encoding the thyroid hormone transporting monocarboxylate transporter (MCT)-8 suffer from a severe form of psychomotor retardation and exhibit abnormal serum thyroid hormone levels. The thyroidal phenotype characterized by high-serum T(3) and low-serum T(4) levels is also found in mice mutants deficient in MCT8 although the cause of these abnormalities is still unknown. Here we describe the consequences of MCT8 deficiency for renal thyroid hormone transport, metabolism, and function by studying MCT8 null mice and wild-type littermates. Whereas serum and urinary parameters do not indicate a strongly altered renal function, a pronounced induction of iodothyronine deiodinase type 1 expression together with increased renal T(3) and T(4) content point to a general hyperthyroid state of the kidneys in the absence of MCT8. Surprisingly, accumulation of peripherally injected T(4) and T(3) into the kidneys was found to be enhanced in the absence of MCT8, indicating that MCT8 deficiency either directly interferes with the renal efflux of thyroid hormones or activates indirectly other renal thyroid hormone transporters that preferentially mediate the renal uptake of thyroid hormones. Our findings indicate that the enhanced uptake and accumulation of T(4) in the kidneys of MCT8 null mice together with the increased renal conversion of T(4) into T(3) by increased renal deiodinase type 1 activities contributes to the generation of the low-serum T(4) and the increase in circulating T(3) levels, a hallmark of MCT8 deficiency.

Original languageEnglish
Issue number2
Pages (from-to)802-9
Number of pages8
Publication statusPublished - 02.2010


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