Issue 8, 2010
From the journal:

Molecular BioSystems

Transport of thyroid hormones is selectively inhibited by 3-iodothyronamine†‡

Alexandra G. Ianculescu,a   Edith C. H. Friesema,b   Theo J. Visser,b   Kathleen M. Giacominic  and  Thomas S. Scanlan*d  

* Corresponding authors

a Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, California, USA

b Department of Internal Medicine, Erasmus University Medical Center Rotterdam, The Netherlands

c Department of Biopharmaceutical Sciences, University of California at San Francisco, San Francisco, California, USA

d Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon, USA
E-mail: scanlant@ohsu.edu
Fax: +1 (503) 494-9275
Tel: +1 (503) 494-9292

Abstract

Thyroid hormone transporters are responsible for the cellular uptake of thyroid hormones, which is a prerequisite for their subsequent metabolism and action at nuclear thyroid hormone receptors. A recently discovered thyroid hormone derivative, 3-iodothyronamine (T1AM), has distinct biological effects that are opposite those of thyroid hormone. Here we investigate the effects of T1AM on thyroid hormone transporters using COS-1 cells transfected with the multispecific organic anion transporting polypeptides (OATPs) 1A2, 1B3, and 1C1, as well as the specific thyroid hormone transporters MCT8 and MCT10, and show that T1AM displays differential inhibition of T3 and T4 cellular uptake by these transporters. T1AM inhibits T3 and T4 transport by OATP1A2 with IC50 values of 0.27 and 2.1 μM, respectively. T4 transport by OATP1C1, which is thought to play a key role in thyroid hormone transport across the blood-brain barrier, is inhibited by T1AM with an IC50 of 4.8 μM. T1AM also inhibits both T3 and T4 uptake via MCT8, the most specific thyroid hormone transporter identified to date, with IC50 values of 95 and 31 μM, respectively. By contrast, T1AM has no effect on thyroid hormone transport by OATP1B3 and MCT10. Given that OATP1A2, OATP1C1, and MCT8 are all present in the brain, T1AM may play an important role in modulating thyroid hormone delivery and activity in specific target regions in the central nervous system.

Graphical abstract: Transport of thyroid hormones is selectively inhibited by 3-iodothyronamine

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Article information

DOI
https://doi.org/10.1039/B926588K
Article type
Paper
Submitted
16 Dec 2009
Accepted
04 Mar 2010
First published
31 Mar 2010

Mol. BioSyst., 2010,6, 1403-1410

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Transport of thyroid hormones is selectively inhibited by 3-iodothyronamine

A. G. Ianculescu, E. C. H. Friesema, T. J. Visser, K. M. Giacomini and T. S. Scanlan, Mol. BioSyst., 2010, 6, 1403 DOI: 10.1039/B926588K

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