Could T1AM induce peripheric thyroid resistance? Minireview: 3-Iodothyronamine (T1AM): a new player on the thyroid endocrine team? Scanlan TS1. 2009 Abstract 3-Iodothyronamine (T(1)AM) is an endogenous compound with chemical features that are similar to thyroid hormone. T(1)AM has a carbon skeleton identical to that of T(4) and contains a single carbon-iodine bond. Theoretically, T(1)AM could be produced from T(4) by enzymatic decarboxylation and deiodination. Recent studies show that T(1)AM and higher iodinated thyronamines are subject to similar metabolic processing as iodothyronines such as T(4), suggesting a biological linkage between iodothyronines and iodothyronamines. In addition, single doses of T(1)AM administered to rodents induce a hypometabolic state that in certain ways resembles hibernation and is opposite to the effects of excess T(4). This review will discuss the latest developments on this recently discovered thyroid hormone derivative. Transport of thyroid hormones is selectively inhibited by 3-iodothyronamine 2010 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.