Journal
ENDOCRINOLOGY
Volume 153, Issue 3, Pages 1528-1537Publisher
ENDOCRINE SOC
DOI: 10.1210/en.2011-1633
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Funding
- Deutsche Forschungsgemeinschaft [HE3848/5-1]
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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 renal and hepatic deiodinase type 1 expression levels were indistinguishable between Oatp1c1 KO mice and control animals. Hypothalamic TRH and pituitary TSH 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. (Endocrinology 153: 1528-1537, 2012)
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