The monocarboxylate transporter 8 (MCT8) linked to human psychomotor retardation is highly expressed in thyroid hormone-sensitive neurons

Abstract

Absence of thyroid hormones (TH) during brain development leads to severe neurological manifestations known as cretinism. As one putative mechanism causing this syndrome, an impaired TH transport across cell membranes that prevents intracellular TH action has been proposed. Recently, a form of X-linked mental retardation combined with elevated serum T3 levels was diagnosed in several human patients. Genetically, this condition could be linked to mutations in the monocarboxylate transporter 8 (MCT8) gene. Since MCT8 has been shown to be an active and specific TH transporter, it might fulfill a unique function in providing TH access to the brain. Here, we studied the expression pattern of MCT8 in the murine CNS by in situ hybridization histochemistry (ISH). In addition to the choroid plexus, highest transcript levels were found in neo- and allocortical regions (namely in the olfactory bulb, cerebral cortex, hippocampus, and the amygdala). Moderate signal intensities were observed in the striatum and in the cerebellum, whereas low levels were detected in a few neuroendocrine hypothalamic nuclei. The transcript levels were not altered in athyroid Pax8-/- mice suggesting that MCT8 expression is not affected by the thyroid status. Comparison of deiodinase type II (D2) and MCT8 localization revealed a rather complementary expession pattern, an observation that argues against a role of MCT8 as a carrier for the prohormone T4 into astrocytes but favors a function as an important transporter for T3 into its neuronal target cell.