The background of the study. Most actions of thyroid hormone, in the form of triiodothyronine (T3), are mediated by changes in gene activity, and the changes take hours or days. Some actions of thyroid hormone are rapid, and presumably non-gene-based. Thyronamines, which are decarboxylated and deiodinated derivatives of T3 may mediate these latter actions. This study evaluated the actions of iodothyronamines and their detection in animal tissues.
How the study was done and the results of the study. Thyronamine (T0-amine) and several iodothyronamines stimulated cyclic AMP production by kidney cells with type 1 trace amine receptors (TAR1), a member of a family of receptors that are activated by biogenic amines. The stimulation was dose-dependent, and there was no stimulation of cells with dopamine or adrenergic receptors. T0-amine and T1-amine did not activate T3 nuclear receptors, and T3 and thyroxine (T4) did not activate TAR1 receptors.
T0-amine and T1-amine were isolated from extracts of mouse brain, heart, liver, and blood. Administration of these two substances to mice resulted in hypothermia (temperature fall from 37°C to 29.5°C in 2 hours), inactivity, and a hunched-back posture lasting 6 to 8 hours. T0-amine and T1-amine slowed the heart rate in mice in 10 minutes, and this effect also lasted for 6 to 8 hours.
Conclusion T0-amine and T1-amine are naturally occurring derivatives of T4 and T3 that act rapidly to inhibit neural and cardiac activity.
The original article. Scanlan TS, Suchland KL, Hart ME, Chiellini G, Huang Y, Kruzich PJ, Frascarelli S, Crossley DA, Bunzow JR, Ronca-Testoni S, Lin ET, Hatton D, Zucchi R, Grandy DK. 3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone. Nat Med 2004;10:638-42.