Thyroid hormone transport and metabolism by OATP1C1 and consequences of genetic variation

Wendy M van der Deure, Pia Skov Hansen, Robin P Peeters, Kirsten Ohm Kyvik, Edith C H Friesema, Laszlo Hegedüs, Theo J Visser

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Udgivelsesdato: Jun-19
OriginalsprogEngelsk
TidsskriftEndocrinology
ISSN0013-7227
DOI
StatusUdgivet - 19. jun. 2008

Fingeraftryk

Iodide Peroxidase
Catalytic Domain
Serum
thyroxine sulfate
In Vitro Techniques

Citer dette

van der Deure, W. M., Hansen, P. S., Peeters, R. P., Kyvik, K. O., Friesema, E. C. H., Hegedüs, L., & Visser, T. J. (2008). Thyroid hormone transport and metabolism by OATP1C1 and consequences of genetic variation. Endocrinology. https://doi.org/10.1210/en.2008-0430
van der Deure, Wendy M ; Hansen, Pia Skov ; Peeters, Robin P ; Kyvik, Kirsten Ohm ; Friesema, Edith C H ; Hegedüs, Laszlo ; Visser, Theo J. / Thyroid hormone transport and metabolism by OATP1C1 and consequences of genetic variation. I: Endocrinology. 2008.
@article{3818b870692a11ddb1a1000ea68e967b,
title = "Thyroid hormone transport and metabolism by OATP1C1 and consequences of genetic variation",
abstract = "OATP1C1 has been characterized as a specific thyroid hormone transporter. Based on its expression in capillaries in different brain regions, OATP1C1 is thought to play a key-role in transporting thyroid hormone across the blood-brain barrier. For this reason, we studied the specificity of iodothyronine transport by OATP1C1 in detail by analysis of thyroid hormone uptake in OATP1C1-transfected COS1 cells. Furthermore, we examined whether OATP1C1 is rate-limiting in subsequent thyroid hormone metabolism in cells co-transfected with deiodinases. We also studied the effect of genetic variation in the OATP1C1 gene: polymorphisms were determined in 155 blood donors and 1192 Danish twins, and related to serum thyroid hormone levels. In vitro effects of the polymorphisms were analyzed in cells transfected with the variants. Cells transfected with OATP1C1 showed increased transport of T4 and T4 sulfate (T4S), little transport of rT3 and no transport of T3 or T3S compared to mock transfected cells. Metabolism of T4, T4S and rT3 by co-transfected deiodinases was greatly augmented in the presence of OATP1C1. The OATP1C1-intron3C>T, Pro143Thr and C3035T polymorphisms were not consistently associated with TH levels, nor did they affect transport function in vitro. In conclusion, OATP1C1 mediates transport of T4, T4S and rT3 and increases the access of these substrates to the intracellular active sites of the deiodinases. No effect of genetic variation on the function of OATP1C1 was observed.",
author = "{van der Deure}, {Wendy M} and Hansen, {Pia Skov} and Peeters, {Robin P} and Kyvik, {Kirsten Ohm} and Friesema, {Edith C H} and Laszlo Heged{\"u}s and Visser, {Theo J}",
year = "2008",
month = "6",
day = "19",
doi = "10.1210/en.2008-0430",
language = "English",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "Heinemann",

}

Thyroid hormone transport and metabolism by OATP1C1 and consequences of genetic variation. / van der Deure, Wendy M; Hansen, Pia Skov; Peeters, Robin P; Kyvik, Kirsten Ohm; Friesema, Edith C H; Hegedüs, Laszlo; Visser, Theo J.

I: Endocrinology, 19.06.2008.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Thyroid hormone transport and metabolism by OATP1C1 and consequences of genetic variation

AU - van der Deure, Wendy M

AU - Hansen, Pia Skov

AU - Peeters, Robin P

AU - Kyvik, Kirsten Ohm

AU - Friesema, Edith C H

AU - Hegedüs, Laszlo

AU - Visser, Theo J

PY - 2008/6/19

Y1 - 2008/6/19

N2 - OATP1C1 has been characterized as a specific thyroid hormone transporter. Based on its expression in capillaries in different brain regions, OATP1C1 is thought to play a key-role in transporting thyroid hormone across the blood-brain barrier. For this reason, we studied the specificity of iodothyronine transport by OATP1C1 in detail by analysis of thyroid hormone uptake in OATP1C1-transfected COS1 cells. Furthermore, we examined whether OATP1C1 is rate-limiting in subsequent thyroid hormone metabolism in cells co-transfected with deiodinases. We also studied the effect of genetic variation in the OATP1C1 gene: polymorphisms were determined in 155 blood donors and 1192 Danish twins, and related to serum thyroid hormone levels. In vitro effects of the polymorphisms were analyzed in cells transfected with the variants. Cells transfected with OATP1C1 showed increased transport of T4 and T4 sulfate (T4S), little transport of rT3 and no transport of T3 or T3S compared to mock transfected cells. Metabolism of T4, T4S and rT3 by co-transfected deiodinases was greatly augmented in the presence of OATP1C1. The OATP1C1-intron3C>T, Pro143Thr and C3035T polymorphisms were not consistently associated with TH levels, nor did they affect transport function in vitro. In conclusion, OATP1C1 mediates transport of T4, T4S and rT3 and increases the access of these substrates to the intracellular active sites of the deiodinases. No effect of genetic variation on the function of OATP1C1 was observed.

AB - OATP1C1 has been characterized as a specific thyroid hormone transporter. Based on its expression in capillaries in different brain regions, OATP1C1 is thought to play a key-role in transporting thyroid hormone across the blood-brain barrier. For this reason, we studied the specificity of iodothyronine transport by OATP1C1 in detail by analysis of thyroid hormone uptake in OATP1C1-transfected COS1 cells. Furthermore, we examined whether OATP1C1 is rate-limiting in subsequent thyroid hormone metabolism in cells co-transfected with deiodinases. We also studied the effect of genetic variation in the OATP1C1 gene: polymorphisms were determined in 155 blood donors and 1192 Danish twins, and related to serum thyroid hormone levels. In vitro effects of the polymorphisms were analyzed in cells transfected with the variants. Cells transfected with OATP1C1 showed increased transport of T4 and T4 sulfate (T4S), little transport of rT3 and no transport of T3 or T3S compared to mock transfected cells. Metabolism of T4, T4S and rT3 by co-transfected deiodinases was greatly augmented in the presence of OATP1C1. The OATP1C1-intron3C>T, Pro143Thr and C3035T polymorphisms were not consistently associated with TH levels, nor did they affect transport function in vitro. In conclusion, OATP1C1 mediates transport of T4, T4S and rT3 and increases the access of these substrates to the intracellular active sites of the deiodinases. No effect of genetic variation on the function of OATP1C1 was observed.

U2 - 10.1210/en.2008-0430

DO - 10.1210/en.2008-0430

M3 - Journal article

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

ER -