Classical thyroid hormones implement a very flexible signaling mechanism. Basically, they comprise two aromatic rings that are connected via an oxygen atom. Optionally, they may contain organic side chains and inorganic iodine atoms.
In the case of iodothyronines, which are represented e.g. by the well-known thyroid hormones T4, T3 and 3,5-T2, the side chain contains an amino group and a carboxylate group. Therefore, iodothyronines are amino acids. Up to four different hydrogen atoms (two at every ring) may be replaced by iodine atoms, and the resulting pattern of iodination determines their biological activity. Generally, iodination of the inner ring and deiodination of the outer ring results in high biological activity (e.g. in T3 and 3,5-T2), whereas iodination of the outer ring and deiodination of the inner ring delivers a receptor-blocking thyroid hormone (e.g. reverse-T3). There are three deiodinases encoded by the DIO1, DIO2 and DIO3 genes that catalyze the "step-up" and "step-down" reactions to active or inactive thyroid hormones, respectively. Multiple molecular processes are able to differentially upregulate and downregulate tissue deiodinases. Therefore, thyroid hormones are subject to both global and local control.
Removal of the amino group results in iodothyroacetates. Their biological effects are similar to those of iodothyronines, but in addition to nuclear receptors they also have a strong effect on membrane-bound receptors, which are only weakly activated by iodothyronines.
Thyronamines lack the carboxylate group. Their biological effect is different to that of iodothyronines and iodothyroacetates. By activating the membrane-bound TAAR1 receptor they have an effect that is in most respects antagonistic to that of classical thyroid hormones. Thyronamines seem to be most active in deiodinated state.
Summarizing, both organic and anorganic modifications are able to modulate the effect of thyroid hormones. This mechanism is a very effective way to encode a high grade of information entropy in rather small molecules.
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