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,

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 folhcular epithelium, special cells (fig.6.2.1) which are large in shape and called parafolhcular (or C) cells are seen. C cells secrete calcitonm. CHEMISTRY The thyroid gland secretes, three hormones-(i) thyroxine, (ii)triiodothyronine and (iii) -calcitonm. Of these three, the bulk is made up of Ihyroxine. In the peripheral tissues, thyroxine is converted into its more active form, tmodothyronine. But it is known that small amounts of tmodothyronine is also produced in the thyroid gland itself. Calcitonin is related to calcium homeostasis and wi be described in detail in connection with parat_hormone and calcium homeostasis (chap.3, sec.VI). Thyroxine (fig.A.6.2.2) Fig.6.2.2. Thyroid hormones Thyroxine contains two phenyl rings linked up by an ether bridge. The left hand side and righ 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 oute 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 Thyroxme wa discovered by Kendal (who, incidentally, also isolated the fundamental corticosteroids) in 1915, but its structural chemistr was established by Harrington in 1926. Tmodothyronine It's structure is otherwise same as T4 but it lacks the iodine atom a 5' of the outer ring (fig. 6.2.2) and consequently it is called T3. Triiodothyronine was discovered and studied extensively in th early 1950s by Gross, Pitt-Rivers and J D Tata. Reverse T3. The iodine at position 5 (of the inner ring) may be absent am the resultant structure is called reverse T3. Reverse T3 is biologically inert. In the blood of the new born, reverse T3 occurs i heavier concentration. BIOSYNTHESIS Fig. 6.2.3. Iodine cycle. [ NB. In this diagram, the nomenclature is as follows : indm = all forms of the element; I- = the ionic form, le, iodide ] The principal events are as follows : Iodine containing foods ar laken 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 folhcular cells are negative (and hence will repel any -vely charged particle like iodide) or (b) mtracellular iodide concentratio is usually higher than that of the plasma (chemical gradient), flow of iodide occurs from blood to the interior of the folhcula cells. This (= iodide trapping), therefore requires energy and comes from break down of ATP. Iodide trapping also involve participation of Nan- K+ ATPase enzyme and supply of oxygen. Perchlorate and pertechnetate ions can compete with iodide for gaming entry into the folhcular cell fie, when these ions are present in sufficient numbers, they rather than the iodides ar Irapped by the folhcular cells). Although use of perchlorate in therapeutics (to reduce thyroxme synthesis in Grave's disease is now obsolete, pertechnatate is used in thyroid imaging procedure, see later, this chapter. TSH strongly facilitates indid Irapping. Iodide trapping also depends strongly upon autoregulation of thyroid (see later, this chapter). Salivary (and also th 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 : Insid Ihe folhcular cell, the Kl is rapidly oxidized to iodine (12). The details are unknown but some known facts are : (a) the oxidatio 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) a intermediate step may be formation of mdinum (l+) ion. (3) Orginfication. The folhcular cells synthesize thyroglobulm whic consists of two subuints of polypeptide chains. In each polypeptide chain, there are several tyrosme (= para hydroxy pheny alanme) molecules. Iodine atoms now attach themselves with the tyrosme molecules to form MIT (monoiodotyrosme) or Dl" (duo doty rosin e) molecules. The MITs or the DITs still remain attached with the thyroglobulm. TSH facilitates this orgamficatio and antithyroids like propylthiouracil inhibits orgamfication. (4) Coupling Two DITs fuse (although the fused complex remain within the thyroglobulm molecule) via an ether bridge (fig. 6. 2. 2), alanine side chain is replaced by a phenolic OH group in th outer (also called p ring, and a molecule of thyroxme (T4) is formed It still remains attached with thyroglobulm. One molecul of DIT and one MIT may also couple to form tmodothyronme (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 facilitate! by TSH and opposed by the antithyroids. The folhcular cell now extrudes little thyroglobulm (containing T4 and T, compounds) into the preexisting colloid of the acinus and the thyroid hormones are stored