The process of fusion (to form T4 or T3) is called coupling.

of the colloid is great, but when it (i.e , the activity) is high, the cells are columnar and the amount of the colloid is reduced. The colloid is made up of a protein, (secreted by the lining cuboidal cells), called, thyroglobulin. Para follicular cells. Occasionally, in between the basement membrane of the follicle and the lining follicular epithelium, special cells (fig. 6.2.1) which are large in shape and called parafollicular (or C) cells are seen. C cells secrete calcitonin. CHEMISTRY The thyroid gland secretes, three hormones-(i) thyroxine, (ii)triiodothyronine and (iii) -calcitonin. Of these three, the bulk is made up of thyroxine. In the peripheral tissues, thyroxine is converted into its more active form, tmodothyronine. But it is known that small amounts of triiodothyronine is also produced in the thyroid gland itself. Calcitonin is related to calcium homeostasis and will be described in detail in connection with parat_hormone and calcium homeostasis (chap 3, sec VI) Thyroxme (figA6 2 2] Fig.6.2.2. Thyroid hormones Thyroxine contains two phenyl rings linked up by an ether bridge. The left hand side and right hand side rings are called the outer and the inner rings respectively. At 3 and 5 (of the inner ring) and 3' and 5' (of the outer ring) positions, iodine atoms are attached. Thus, it contains four iodine atoms and consequently called T4. An alanine mole-cule is attached at position 1 of the inner ring, while the position 4' of the outer ring contains an OH group. Thyroxine was discovered by Kendal (who, incidentally, also isolated the fundamental corticosteroids) in 1915, but its structural chemistry was established by Harrington in 1926. Tmodothyronine It's structure is otherwise same as T4 but it lacks the iodine atom at 5' of the outer ring (fig. 6.2.2) and consequently it is called T3. Triiodothyronine was discovered and studied extensively in the early 1950s by Gross, Pitt-Rivers and J D Tata. Reverse T3. The iodine at position 5 (of the inner ring) may be absent and the resultant structure is called reverse T3. Reverse T3 is biologically inert. In the blood of the new born, reverse T3 occurs in heavier concentration. BIOSYNTHESIS Fig. 6.2.3. Iodine cycle. [ NB. In this diagram, the nomenclature is as follows : indine = all forms of the element; I- = the ionic form, le, iodide. ] The principal events are as follows : Iodine containing foods ar taken converted (reduced) into iodide (Kl) in the gastrointestinal tract reaches the thyroid gland (fig. 6.2.3). Afterwards : (1) From the blood, the Kl is taken up by the folhcular cells of the thyroid, a process called 'iodide trapping', this iodide trappm can occur despite electrical or chemical ('electrochemical) gradient. That is, inspite of the facts that - (a) interior of the follicular cells are negative (and hence will repel any -vely charged particle like iodide) or (b) intracellular iodide concentration is usually higher than that of the plasma (chemical gradient), flow of iodide occurs from blood to the interior of the follicular cells. This (= iodide trapping), therefore requires energy and comes from break down of ATP. Iodide trapping also involves participation of Na+ K+ ATPase enzyme and supply of oxygen. Perchlorate and pertechnetate ions can compete with iodides for gaining entry into the follicular cell (ie, when these ions are present in sufficient numbers, they rather than the iodides are trapped by the follicular cells). Although use of perchlorate in therapeutics (to reduce thyroxine synthesis in Grave's disease) is now obsolete, pertechnatate is used in thyroid imaging procedure, see later, this chapter. TSH strongly facilitates indide trapping. Iodide trapping also depends strongly upon autoregulation of thyroid (see later, this chapter). Salivary (and also the gastric) glands have some power of iodide (or even other halogens, like bromide) trapping. There is an interesting speculation that the iodide trapping is carried out by a carrier and lecithin may be the carrier. (2) Oxidation of iodide : Inside the follicular cell, the Kl is rapidly oxidized to iodine (12). The details are unknown but some known facts are : (a) the oxidation requires an enzyme called 'pero-xidase'. One enzyme which may be the peroxidase has been isolated and it contains, heme; (b),H202 is necessary for the oxidation and is manufactured locally, (c) hydrogen ions are removed by NADPH, (d) an intermediate step may be formation of mdinum (l+) ion. (3) Qrganification. The follicular cells synthesize thyroglobulin which consists of two subunits of polypeptide chains. In each polypeptide chain, there are several tyrosine (= para hydroxy phenyl alanine) molecules. Iodine atoms now attach themselves with the tyrosine molecules to form MIT (monoiodotyrosine) or DlT (diiodotyrosine) molecules. The MITs or the DITs still remain attached with the thyroglobulin. TSH facilitates this organification and antithyroids like propylthiouracil inhibits organification. (4) Coupling. Two DITs fuse (although the fused complex remains within the thyroglobulin molecule) via an ether bridge (fig.6.2.2), alanine side chain is replaced by a phenolic OH group in the outer (also called b ring, and a molecule of thyroxine (T4) is formed. It still remains attached with thyroglobulin. One molecule of DIT and one MIT may also couple to form triiodothyronine (T). The process of fusion (to form T4 or T3) is called coupling. Coupling requires oxidation and presence of the peroxidase mentioned in step 3 (above) is necessary. Coupling is facilitated by TSH and opposed by the antithyroids. The folhcular cell now extrudes little thyroqlobulin (containing T4 and T3 compounds) into the preexisting colloid of the acinus and the thyroid hormones are stored