Thyronamines—Past, Present, and Future

Abstract

Thyronamines (TAMs) are a newly identified class of endogenous signaling compounds. Their structure is identical to that of thyroid hormone and deiodinated thyroid hormone derivatives, except that TAMs do not possess a carboxylate group. Despite some initial publications dating back to the 1950s, TAMs did not develop into an independent area of research until 2004, when they were rediscovered as potential ligands to a class of G protein-coupled receptors called trace-amine associated receptors. Since this discovery, two representatives of TAMs, namely 3-iodothyronamine (3-T(1)AM) and thyronamine (T(0)AM), have been detected in vivo. Intraperitoneal or central injection of 3-T(1)AM or T(0)AM into mice, rats, or Djungarian hamsters caused various prompt effects, such as metabolic depression, hypothermia, negative chronotropy, negative inotropy, hyperglycemia, reduction of the respiratory quotient, ketonuria, and reduction of fat mass. Although their physiological function remains elusive, 3-T(1)AM and T(0)AM have already revealed promising therapeutic potential because they represent the only endogenous compounds inducing hypothermia as a prophylactic or acute treatment of stroke and might thus be expected to cause fewer side effects than synthetic compounds. This review article summarizes the still somewhat scattered data on TAMs obtained both recently and more than 20 yr ago to yield a complete and updated picture of the current state of TAM research.

Translating Pharmacological Findings from Hypothyroid Rodents to Euthyroid Humans: Is There a Functional Role of Endogenous 3,5-T2?

“…This observation is in line with a 3,5-T2-mediated increase in glucose sensitivity described for pharmacological interventions with high doses of 3,5-T2 in animal models (10,11). A possible indication to understand this discrepancy could be an effect of 3-iodothyronamine, which was suggested as a degradation product of 3,5-T2 and exhibited hyperglycemic effects (4,42). An antagonistic link between these two TH…”

“…Recent pharmacological applications of 3,5-T2 mainly in hypothyroid rodent models (3,4) challenged this hypothesis because they revealed rapid and chronic metabolic changes, partly independent of the classical T3 receptors (TR). 3,5-T2 rapidly enhanced hepatic oxygen consumption (5,6), and hepatic mitochondria were identified as specific targets (7,8).…”

ApoB-100-containing Lipoproteins Are Major Carriers of 3-Iodothyronamine in Circulation

“…Anhydrous dimethylformamide (DMF) was obtained by passing through two columns of activated molecular sieves. Final compounds were characterized by 1 H NMR and mass spectrometry.…”

In the brain of mice, 3-iodothyronamine (T1AM) is converted into 3-iodothyroacetic acid (TA1) and it is included within the signaling network connecting thyroid hormone metabolites with histamine

“…Both 3-iodothyronamine (T1AM) and its oxidative metabolite, 3-iodothyroacetic acid (TA1), are members of the large family of thyroid hormone metabolites (Scanlan et al, 2004;Piehl et al, 2011). T1AM circulates in healthy rodents and is accumulated in most tissues, including the brain, where TA1 was also detected (Saba et al, 2010;Musilli et al, 2014).…”