Transport of thyroid hormones is selectively inhibited by 3-iodothyronamine

Alexandra G. Ianculescu, Edith C H Friesema, Theo J. Visser, Kathleen M. Giacomini, Thomas (Tom) Scanlan

Research output: Contribution to journalArticle

20 Citations (Scopus)

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 (T 1AM), has distinct biological effects that are opposite those of thyroid hormone. Here we investigate the effects of T 1AM 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 T 1AM displays differential inhibition of T 3 and T 4 cellular uptake by these transporters. T 1AM inhibits T 3 and T 4 transport by OATP1A2 with IC 50 values of 0.27 and 2.1 μM, respectively. T 4 transport by OATP1C1, which is thought to play a key role in thyroid hormone transport across the blood-brain barrier, is inhibited by T 1AM with an IC 50 of 4.8 μM. T 1AM also inhibits both T 3 and T 4 uptake via MCT8, the most specific thyroid hormone transporter identified to date, with IC 50 values of 95 and 31 μM, respectively. By contrast, T 1AM has no effect on thyroid hormone transport by OATP1B3 and MCT10. Given that OATP1A2, OATP1C1, and MCT8 are all present in the brain, T 1AM may play an important role in modulating thyroid hormone delivery and activity in specific target regions in the central nervous system.

Original languageEnglish (US)
Pages (from-to)1403-1410
Number of pages8
JournalMolecular BioSystems
Volume6
Issue number8
DOIs
StatePublished - Aug 2010

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Thyroid Hormones
3-iodothyronamine
Thyroid Hormone Receptors
COS Cells
Cytoplasmic and Nuclear Receptors
Blood-Brain Barrier
Anions
Central Nervous System
Peptides
Brain

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Biology

Cite this

Ianculescu, A. G., Friesema, E. C. H., Visser, T. J., Giacomini, K. M., & Scanlan, T. T. (2010). Transport of thyroid hormones is selectively inhibited by 3-iodothyronamine. Molecular BioSystems, 6(8), 1403-1410. https://doi.org/10.1039/b926588k

Transport of thyroid hormones is selectively inhibited by 3-iodothyronamine. / Ianculescu, Alexandra G.; Friesema, Edith C H; Visser, Theo J.; Giacomini, Kathleen M.; Scanlan, Thomas (Tom).

In: Molecular BioSystems, Vol. 6, No. 8, 08.2010, p. 1403-1410.

Research output: Contribution to journalArticle

Ianculescu, AG, Friesema, ECH, Visser, TJ, Giacomini, KM & Scanlan, TT 2010, 'Transport of thyroid hormones is selectively inhibited by 3-iodothyronamine', Molecular BioSystems, vol. 6, no. 8, pp. 1403-1410. https://doi.org/10.1039/b926588k
Ianculescu, Alexandra G. ; Friesema, Edith C H ; Visser, Theo J. ; Giacomini, Kathleen M. ; Scanlan, Thomas (Tom). / Transport of thyroid hormones is selectively inhibited by 3-iodothyronamine. In: Molecular BioSystems. 2010 ; Vol. 6, No. 8. pp. 1403-1410.
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