Thyroid gland

Question 1

Synthesis and secretion of T3 and T4

Answer 1

1. Iodide trapping - Thyroid follicular cells trap iodide ions by actively transporting them from the blood into the cytosol.
2. Synthesis of thyroglobulin - While the follicular cells are trapping they are also synthesizing thyroglobulin (TGB) , a large glycoprotein that is produced in the rough endoplasmic reticulum, modified in the Golgi complex, and packaged into secretory vesicles. • The vesicles then undergo exocytosis, which releases TGB into the lumen of the follicle.
3. Oxidation of iodide - Some of the amino acids in TGB are tyrosines that will become iodinated. However, negatively charged iodide ions cannot bind to tyrosine until they un- dergo oxidation (removal of electrons) to iodine: 2 I􏰑 → I2. As the iodide ions are being oxidized, they pass through the membrane into the lumen of the follicle.

4 . Iodination of tyrosine -As iodine molecules (I2) form, they react with tyrosines that are part of thyroglobulin molecules. Binding of one iodine atom yields monoiodotyrosine (T1), and a second iodination produces diiodotyrosine (T2). The TGB with attached iodine atoms, a sticky material that accumulates and is stored in the lumen of the thyroid follicle, is termed colloid. .

5 . Coupling of T1 and T2 -During the last step in the synthesis of thyroid hormone, two T2 molecules join to form T4, or one T1 and one T2 join to form T3

6. Pinocytosis and digestion of colloid - Droplets of colloid re- enter follicular cells by pinocytosis and merge with lyso- somes. Digestive enzymes in the lysosomes break down TGB, cleaving off molecules of T3 and T4.
7. Secretion of thyroid hormones - Because T3 and T4 are lipid- soluble, they diffuse through the plasma membrane into in- terstitial fluid and then into the blood. T4 normally is secreted in greater quantity than T3, but T3 is several times more po- tent. Moreover, after T enters a body cell, most of it is converted to T3 by removal of one iodine.
8. Transport in the blood -More than 99% of both the T3 and the T4 combine with transport proteins in the blood, mainly thyroxine-binding globulin (TBG)