Figure 2.

The distribution of thyroglobulin protein in thyroid follicles under conditions that are either wildtype (left), or in case of Hypothyroidism with Defective Thyroglobulin (right). In wildtype thyroid (left), Tg is synthesized in the ER of within the thyroid epithelial monolayer. From there, Tg undergoes intracellular trafficking leading to its secretion into the follicular lumen. Secreted Tg serves as the primary substrate of thyroid hormone biosynthesis, utilizing thyroidal iodination machinery that is located at the apical membrane. In hypothyroidism with defective Tg (right), misfolded Tg is blocked in intracellular transport from the ER, inducing ER stress with massive ER expansion. Tg remaining within the ER of the thyroid epithelial monolayer is unavailable for thyroid hormone biosynthesis.