Expression pattern of thyroid hormone transporters in the postnatal mouse brain.

Julia Mã¼Ller,Heike Heuer

doi:10.3389/fendo.2014.00092

Abstract

For a comprehensive description of the tissue-specific thyroidal state under normal as well as under pathophysiological conditions it is of utmost importance to include thyroid hormone (TH) transporters in the analysis as well. The current knowledge of the cell-specific repertoire of TH transporters, however, is still rather limited, although several TH transporting proteins have been identified. Here, we describe the temporal and spatial distribution pattern of the most prominent TH transporters in the postnatal mouse brain. For that purpose, we performed radioactive in situ hybridization studies in order to analyze the cellular mRNA expression pattern of the monocarboxylate transporters Mct8 and Mct10, the L-type amino acid transporters Lat1 and Lat2 as well as the organic anion transporting peptide Oatp1c1 at different postnatal time points. Highest TH transporter expression levels in the CNS were observed at postnatal day 6 and 12, while hybridization signal intensities visibly declined after the second postnatal week. The only exception was Mct10 for which the strongest signals could be observed in white matter regions at postnatal day 21 indicating that this transporter is preferentially expressed in mature oligodendrocytes. Whereas Mct8 and Lat2 showed an overlapping neuronal mRNA expression pattern in the cerebral cortex, hippocampus, and in the hypothalamus, Oatp1c1 and Lat1 specific signals were most prominent in capillary endothelial cells throughout the CNS. In the choroid plexus, expression of three transporters (Mct8, Lat2, and Oatp1c1) could be detected, whereas in other brain areas (e.g., striatum, thalamus, and brain stem nuclei) only one of the transporter candidates appeared to be present. Overall, our study revealed a distinct mRNA distribution pattern for each of the TH transporter candidates. Further studies will reveal to which extent these transporters contribute to the cell-specific TH uptake and efflux in the mouse CNS.

Highlights

Thyroid hormone (TH) action requires the presence of TH transporters that facilitate its cellular uptake and efflux [1,2,3,4]
We aimed to determine the cellular distribution pattern of the transporters Mct8 (Slc16a2), Mct10 (Slc16a10), Lat1 (Slc7a5), Lat2 (Slc7a8), and Oatp1c1 (Slco1c1) that have all been described to facilitate the cellular transport of TH [25]
Brains were collected from C57/Bl6 male mice at postnatal day 6 (P6), P12, P21, and P84 and consecutive frozen brain sections were subjected to the in situ hybridization (ISH) procedure as described previously [24]

Summary

Introduction

Thyroid hormone (TH) action requires the presence of TH transporters that facilitate its cellular uptake and efflux [1,2,3,4]. Immunohistochemical studies and in situ hybridization (ISH) experiments showed pronounced Mct expression in distinct neuronal populations of the cerebral cortex, hippocampus, striatum, hypothalamus, and cerebellum [15], Mct ko mice do not display overt neurological symptoms [11], they faithfully replicate the abnormal serum TH parameters characteristic for human MCT8 deficiency. These Mct ko mice do not show immunohistochemically any abnormalities such as a delayed Purkinje cell development or an altered differentiation of inhibitory neurons in the cerebral cortex, both strong neuronal indicators for TH deprivation [11, 14].

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