Figure 2.

Overview of the main players in thyroid follicular cell function. Schematic diagram of a thyroid follicular cell and the main proteins involved in the synthesis, storage, and release into bloodstream of the thyroid hormones triiodothyronine (T3) and thyroxine (T4). At the basolateral membrane, circulating iodide (I^-) is actively taken-up by the Nis symporter. It then passively diffuses to the apical membrane where it is actively transported to the lumen by Pendrin and other transporters. Once I^- is oxidized by thyroid peroxidase (Tpo), using H₂O₂ generated by the oxidase Duox2, tyrosine residues in thyroglobulin (Tg) are iodinated to form mono-iodotyrosine (MIT) and/or di-iodotyrosine (DIT), whose coupling yields thyroid hormones. Colloid droplets rich in Tg are endocytosed into the thyroid follicular cell, where Tg lysosomal proteolysis releases MIT, DIT, T4, and T3. Thyroid hormones are transported to circulation by the monocarboxylate transporter 8 (Mct8), whereas I^- from MIT and DIT is recycled by the iodotyrosine deiodinase (Dehal1). All of these processes rely on the co-existence of the thyroid transcription factors Nkx2-1, Foxe1, Pax8 and Hhex, in the nucleus of the thyroid follicular cell, from where they regulate the expression of genes such as Slc5a5, Tpo, Tg and Tshr. Also, in the basolateral membrane, TSH, IGF1 and TGFβ trigger the main pathways involved in adult maintenance of thyroid differentiation by cAMP, PI3K and SMAD activation, respectively.