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

S Mayerl, TJ Visser, VM Darras, S Horn… - Endocrinology, 2012 - academic.oup.com
S Mayerl, TJ Visser, VM Darras, S Horn, H Heuer
Endocrinology, 2012academic.oup.com
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 T4. In the
rodent brain, Oatp1c1 is highly enriched in capillary endothelial cells and choroid plexus
structures where it may mediate the entry of T4 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 …
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 T4. In the rodent brain, Oatp1c1 is highly enriched in capillary endothelial cells and choroid plexus structures where it may mediate the entry of T4 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 T3 and T4 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 T4 and T3 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 T3 in the brain were down-regulated. This central nervous system-specific hypothyroidism is presumably caused by an impaired passage of T4 across the blood-brain barrier and indicates a unique function of Oatp1c1 in facilitating T4 transport despite the presence of other thyroid hormone transporters such as Mct8.
Oxford University Press