Thyroid hormone is a major determinant of tissue functions in vivo. Within the tissues, cells are not passive players in the process of hormonal signaling since they can actively customize hormonal action. Triiodothyronine (T3), the active form of thyroid hormone is produced predominantly outside the thyroid parenchyma secondary to peripheral tissue deiodination of thyroxine (T4), with <20% being secreted directly from the thyroid. Upon entering the cells via specific transporters, thyroid hormone is modified via the action of selenoenzymes known as deiodinases.
While the type II deiodinase (D2) converts the prohormone thyroxine (T4) to the biologically active T3, the type III deiodinase (D3) converts it to reverse T3, an inactive metabolite. D3 also inactivates T3 to T2, terminating thyroid hormone action. Therefore, deiodinases provides cells with the ability to reduce intracellular thyroid signaling or produce extra amounts of T3. This precise control of the T3-dependent transcriptional program is required by multiple organs and cell systems, including the stem and the neoplastic cells. In this context, the identification of a close connection between thyroid hormones and different signal pathways involved in the control of cell functions suggested that the deiodinases may play a role in the definition of cell biology and physiology in normal and pathological context.
Deciphering how all these events are achieved, how the T3 signal is controlled and integrated in stem cells and their niches, and how it can impact on them is essentially unknown and represents a challenge for coming years.