 Hello and welcome to Physiology Open. Before we go to the video, state whether following statements are true or false regarding synthesis of thyroid hormones. You can pause the video and think about the question. We will come back to the question at the end of the video again. Now let's see the concepts on mechanism of synthesis of thyroid hormones. Thyroid hormones are iodinated tyrosines which is an amino acid. Thyroid gland synthesizes these hormones from two substrate, the iodine and the protein thyroglobulin which is a tyrosine amino acid rich protein. This protein is synthesized by the epithelial cells in lining the thyroid follicles and is stored in the colloid. For synthesis of thyroid hormones to occur, thyroid follicular cells should also capture the iodide from blood, transport it to colloid and cause binding of the iodine to the tyrosine residues of the thyroglobulin protein. For release of thyroid hormones, follicular cells should take this iodinated substance from the colloid, separate the thyroid hormones from thyroid globulin and release them into the blood. So synthesis of thyroid hormone takes place in several steps. We will see each one of them separately. So here is shown a diagram of the follicles of the thyroid gland. If we magnify this portion, we can represent it in a diagram like this where this side depicts the colloid, this side is the basolateral side with blood vessels and this represents the epithelial cell lining the follicles or tyrosides. The membrane of the epithelial cell facing towards the colloid is a pical membrane while the other sides are the basolateral membrane. So now let's talk about the steps of synthesis of thyroid hormones. First step is synthesis of thyroglobulin. Thyroglobulin is synthesized by follicular epithelial cells just like any other protein synthesis by cells and is secreted into the colloid by exocytosis. So this protein is stored in the colloid. The next step involves trapping and transport of iodide. Iodine is present in circulation as iodide ion. This iodide is taken up into the cytoplasm by sodium iodide simporter which is a secondary active transporter. This is present on the basolateral membrane of thyrocytes. This iodide then enters into the colloid via the epical membrane through chloride iodide exchanger which is also known as pendrine. So now we got both iodide and thyroglobulin into the colloid. However the iodide cannot react with the tyrosine residues. For that it should be oxidized to iodine. So this process of oxidation of iodide to iodine and iodination of the tyrosine residues of the tyroglobulin is known as organification. This occurs in presence of the enzyme thyroid peroxidase present on the epical membrane of thyrocytes. So organification is the third step. Many tyrosine residues of tyroglobulin are iodinated either at single site forming monoiodotyrocenes that is MIT or two sites forming diiodotyrocenes that is DIT. Now these MIT and DIT are not thyroid hormones. It is the coupling or combination of these iodinated tyrosines which produces thyroid hormones. One MIT and one DIT coupled to form triiodothyronine that is T3 and two DITs coupled to form tetraiodothyronine that is T4 or thyroxine. Now this reaction also occurs in presence of the same enzyme that is thyroid peroxidase. This is known as coupling reaction. So basically thyroid hormones form within the thyroglobulin molecule. Now when the gland is stimulated by thyroid-stimulating hormone that is TSH from the pituitary, all these steps of synthesis of thyroid hormones that is synthesis of thyroglobulin, uptake of iodide, organification, coupling reaction all are stimulated. Also the follicular cells start taking up the stored iodinated thyroglobulin from the colloid by endocytosis. When taken up inside the cytoplasm, lysosomes fuse with the phagocytosed thyroglobulin and cleave T3 and T4 from thyroglobulin by proteases which are then released from the basolateral site and enter into the circulation. Now these proteases also separate the amino acids which are reused to produce thyroglobulin. The MIT and DIT which are not coupled are acted upon by the enzyme deiodinase which as its name suggests detaches the iodine from the tyrosine both of which are recycled. Now let's come back to our original question. Now see we have seen that thyroid peroxidase is responsible for three steps oxidation of iodide to iodine reaction of iodine with thyroglobulin which are together are known as organification and it is also required for coupling of MIT and DIT. So drugs which inhibit this enzyme will interfere with all these steps of thyroid hormone synthesis. So first statement is true. Well in second statement see thyroid peroxidase oxidizes iodide to iodine which combines with thyroglobulin and not iodine to iodide as mentioned in this statement. So second statement is a false statement. Okay thanks for watching the video. If you liked it do not forget to subscribe to the channel Physiology Open. Thank you.