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Departments of Internal Medicine (E.C.H.F., R.D., E.P.C.M.M., E.P.K., T.J.V.) and Nuclear Medicine (E.P.K., G.H.), Erasmus University Medical Center, 3015 GE Rotterdam, The Netherlands; and Institute of Physiology, University of Zürich (F.V.), CH-8057 Zürich, Switzerland
Address all correspondence and requests for reprints to: Theo J. Visser, Ph.D., Department of Internal Medicine, Erasmus University Medical Center, Room Bd234, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. E-mail: visser{at}inw3.azr.nl
Transport of thyroid hormone across the cell membrane is required
for thyroid hormone action and metabolism. We have investigated the
possible transport of iodothyronines by the human system L amino acid
transporter, a protein consisting of the human 4F2 heavy chain and the
human LAT1 light chain. Xenopus oocytes were injected
with the cRNAs coding for human 4F2 heavy chain and/or human LAT1 light
chain, and after 2 d were incubated at 25 C with 0.01–10
µM [125I]T4,
[125I]T3,
[125I]rT3, or
[125I]3,3'-diiodothyronine or with 10–100
µM [3H]arginine, [3H]leucine,
[3H]phenylalanine, [3H]tyrosine, or
[3H]tryptophan. Injection of human 4F2 heavy chain cRNA
alone stimulated the uptake of leucine and arginine due to dimerization
of human 4F2 heavy chain with an endogenous Xenopus
light chain, but did not affect the uptake of other ligands. Injection
of human LAT1 light chain cRNA alone did not stimulate the uptake of
any ligand. Coinjection of cRNAs for human 4F2 heavy chain and human
LAT1 light chain stimulated the uptake of phenylalanine >
tyrosine > leucine > tryptophan (100 µM) and
of 3,3'-diiodothyronine > rT3 
T3 >
T4 (10 nM), which in all cases was
Na+ independent. Saturation analysis provided apparent
Michaelis constant (Km) values of 7.9 µM for
T4, 0.8 µM for T3, 12.5
µM for rT3, 7.9 µM for
3,3'-diiodothyronine, 46 µM for leucine, and 19
µM for tryptophan. Uptake of leucine, tyrosine, and
tryptophan (10 µM) was inhibited by the different
iodothyronines (10 µM), in particular T3.
Vice versa, uptake of 0.1 µM
T3 was almost completely blocked by coincubation with 100
µM leucine, tryptophan, tyrosine, or phenylalanine.
Our results demonstrate stereospecific Na+-independent transport of iodothyronines by the human heterodimeric system L amino acid transporter.
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