Cited by 396Thyroid Disorders and TreatmentsDrug Transport and Resistance MechanismsIon Transport and Channel Regulation

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Plasma Membrane Transport of Thyroid Hormones and Its Role in Thyroid Hormone Metabolism and Bioavailability

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Hennemann, Georg, Docter, Roelof, Friesema, Edith C. H., de Jong, Marion, Krenning, Eric P., Visser, Theo J.·2001·Endocrine Reviews

DOI 10.1210/edrv.22.4.0435

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Abstract

Although it was originally believed that thyroid hormones enter target cells by passive diffusion, it is now clear that cellular uptake is effected by carrier-mediated processes. Two stereospecific binding sites for each T4 and T3 have been detected in cell membranes and on intact cells from humans and other species. The apparent Michaelis-Menten values of the high-affinity, low-capacity binding sites for T4 and T3 are in the nanomolar range, whereas the apparent Michaelis- Menten values of the low-affinity, high-capacity binding sites are usually in the lower micromolar range. Cellular uptake of T4 and T3 by the high-affinity sites is energy, temperature, and often Na+ dependent and represents the translocation of thyroid hormone over the plasma membrane. Uptake by the low-affinity sites is not dependent on energy, temperature, and Na+ and represents binding of thyroid hormone to proteins associated with the plasma membrane. In rat erythrocytes and hepatocytes, T3 plasma membrane carriers have been tentatively identified as proteins with apparent molecular masses of 52 and 55 kDa. In different cells, such as rat erythrocytes, pituitary cells, astrocytes, and mouse neuroblastoma cells, uptake of T4 and T3 appears to be mediated largely by system L or T amino acid transporters. Efflux of T3 from different cell types is saturable, but saturable efflux of T4 has not yet been demonstrated. Saturable uptake of T4 and T3 in the brain occurs both via the blood-brain barrier and the choroid plexus-cerebrospinal fluid barrier. Thyroid hormone uptake in the intact rat and human liver is ATP dependent and rate limiting for subsequent iodothyronine metabolism. In starvation and nonthyroidal illness in man, T4 uptake in the liver is decreased, resulting in lowered plasma T3 production. Inhibition of liver T4 uptake in these conditions is explained by liver ATP depletion and increased concentrations of circulating inhibitors, such as 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid, indoxyl sulfate, nonesterified fatty acids, and bilirubin. Recently, several organic anion transporters and L type amino acid transporters have been shown to facilitate plasma membrane transport of thyroid hormone. Future research should be directed to elucidate which of these and possible other transporters are of physiological significance, and how they are regulated at the molecular level.

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“As one of the possible causes of true malabsorption, interrupted function or expression of ileal LT4 transporters has been proposed (18).”
Background

Authors: Hennemann, G., Docter, R., Friesema, E. C. H., de Jong, M., Krenning, E. P., & Visser, T. J.
Affiliations: Erasmus MC (NL)
Department of Internal Medicine (R.D., E.C.H.F., T.J.V.), Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands
Department of Nuclear Medicine (G.H., M.d.J., E.P.K.), Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands
ORCID: Friesema, Edith C. H.
Krenning, Eric P.
Venue: Endocrine Reviews
Publisher: The Endocrine Society
Published: 2001-08-01
Volume: 22
Issue: 4
Pages: 451-476
ISSN: 0163-769X (ISSN-L)
1945-7189
DOI: 10.1210/edrv.22.4.0435
OpenAlex: W2108671981
Cited by: 394
References: 255
Citations by year: 2026: 5 · 2025: 5 · 2024: 7 · 2023: 14 · 2022: 12 · 2021: 8 · 2020: 14 · 2019: 19 · 2018: 13 · 2017: 16 · 2016: 21 · 2015: 17 · 2014: 18 · 2013: 23 · 2012: 15
FWCI: 2.00
Type: journal article
Language: en
Open access: green
hdl.handle.net
Licence: other-oa
Locations: Endocrine Reviews (publishedVersion)
PubMed (publishedVersion)
EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
Keywords: thyroid hormone transport, plasma membrane transport, thyroid hormone uptake, triiodothyronine, thyroxine, carrier-mediated transport, system L amino acid transporter, organic anion transporters, blood-brain barrier, low T3 syndrome, starvation
MeSH terms: Animals, Binding Sites, Biological Availability, Biological Transport, Active, Brain, Carrier Proteins, Cell Membrane, Humans, Species Specificity, Starvation, Thyroid Hormones, Hepatocytes

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Plasma Membrane Transport of Thyroid Hormones and Its Role in Thyroid Hormone Metabolism and Bioavailability

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