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.,
Molecular BioSystems
Department of Internal Medicine

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