title: Impact of Oatp1c1 deficiency on thyroid hormone metabolism and action in the mouse brain.
abstract: 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.
authors.affiliation: Leibniz Institute for Age Research/Fritz Lipmann Institute e.V., Beutenbergstrasse 11, D-07745 Jena/Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Mayerl
authors.forename: Theo J
authors.initials: TJ
authors.lastname: Visser
authors.forename: Veerle M
authors.initials: VM
authors.lastname: Darras
authors.forename: Sigrun
authors.initials: S
authors.lastname: Horn
authors.forename: Heike
authors.initials: H
authors.lastname: Heuer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D001921:Brain / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D007037:Hypothyroidism / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D027701:Organic Cation Transport Proteins / Q000172:deficiency*; D013963:Thyroid Hormones / Q000378:metabolism*; D013974:Thyroxine / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism
chemical_list: C464433:Oatp2 protein, mouse; D027701:Organic Cation Transport Proteins; D013963:Thyroid Hormones; D014284:Triiodothyronine; D013974:Thyroxine