Impact of Oatp1c1 deficiency on thyroid hormone metabolism and action in the mouse brain

Organic anion-transporting polypeptide 1c1 (Oatp1c1) (also known as Slco1c1 and Oatp14) belongs to the family of Oatp and has been shown to facilitate the transport of T 4. In the rodent brain, Oatp1c1 is highly enriched in capillary endothelial cells and choroid plexus structures where it may mediate the entry of T 4 into the central nervous system. Here, we describe the generation and first analysis of Oatp1c1-deficient mice. Oatp1c1 knockout (KO) mice were born with the expected frequency, were not growth retarded, and developed without any overt neurological abnormalities. Serum T 3 and T 4 concentrations as well as renalandhepatic deiodinase type 1 expression levels were indistinguishable between Oatp1c1 KO mice and control animals. Hypothalamic TRH and pituitaryTSH mRNA levels were not affected, but brain T 4 and T 3 content was decreased in Oatp1c1-deficient animals. Moreover, increased type 2 and decreased type 3 deiodinase activities indicate a mild hypothyroid situation in the brain of Oatp1c1 KO mice. Consequently, mRNA expression levels of gene products positively regulated by T 3 in the brain were down-regulated. This central nervous system-specific hypothyroidism is presumably caused by an impaired passage of T 4 across the blood-brain barrier and indicates a unique function of Oatp1c1 in facilitating T 4 transport despite the presence of other thyroid hormone transporters such as Mct8. Copyright

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