The below mentioned article provides an overview on Triodothyronine (T3) and Tetraiodothyronine (T4) Hormones. After reading this article you will learn about: 1. Meaning of T3 and T4 Hormones 2. Biosynthesis of T3 and T4 Hormones 3. Transport 4. Catabolism 5. Control of Secretion.
Meaning of T3 and T4 Hormones:
T3 and T4 are popularly known as triiodothyronine and tetraiodothyronine or thyroxine respectively. These hormones are secreted from principal follicular cells of thyroid gland. Kendall (1918) isolated the active component of the thyroid that he named thyroxine. In 1952, triiodothyronine was found to be more active than thyroxine. These hormones are iodo amino acid hormones.
Biosynthesis of T3 and T4 Hormones:
T3 and T4 are iodinated derivatives of amino acid tyrosine. These hormones are unique in that they are complexed through covalent bonds to iodine.
Biosynthesis of thyroid hormones are describe below:
1. Trapping of Iodide:
Thyroid follicular cells collect inorganic iodide (I–) from blood against steep electrochemical gradients with the help of carrier protein. (Sodium iodide symporter) located in the basal plasma membrane in association with Na+-K+-ATPase. This is known as “iodite pump”.
The carrier protein carriers iodide (l–) while ATPase causes (i) breakdown of ATP into ADP and Pi to derive energy for iodine transport and (ii) a simultaneous exchange of Na+ and K+ ions between the cells and extracellular fluid. The concentration for iodide achieved by the normal thyroid is 20:1, or more, over the blood plasma. Within 1 5 minutes, after administration radioactivity in the thyroid is present in organic compounds.
2. Oxidation of Iodide:
Next inorganic iodites (I–) are oxidized into “active iodine or l+/IO– or iodinium ions” through removal of electrons within the follicular cells in presence of enzyme, tetrameric-heme-enzyme called thyroid peroxidase. This enzyme uses H2O2 as a co-substrate. This reaction is chiefly occurred in the microvilli of the follicular cells.
3. lodination of Tyrosine:
The follicular cells synthesis a glycoprotein, thyroglobulin (mol. wt. 669 kdt) which contains 115 tyrosine residues. Thyroglobulin passes into the colloid by the process of exocytosis. In inorganic iodide that accumulates in the follicular epithelium is oxidized to l2 (elemental iodine) or IO–. At the follicular cell membrane colloid interface, thyroperoxidase utilizes the active iodides for iodination of some of the tyrosine residues of thyroglobulin molecules of colloid.
MIT or 3-monoiodotyrosine is produced when one iodine replaces a hydrogen at C3 of the phenyl ring of a tyrosine and DIT or 3’5-diiodotyrosine is produced if two iodine’s replaces two hydrogen’s at C3 and C5 of phenyl ring of tyrosine. Most of the iodide in thyroglobulin is not in iodothyronine; about 70% is in inactive compounds MIT and DIT.
4. Coupling of Iodotyrosines:
Now, within thyroglobulin molecules, either DIT is oxidatively coupled with another DIT residue to form T4 or a DIT is oxidatively coupled with a MIT to form T3. The coupling is mediated by thyroperoxidase again. During this coupling, an alanine is cleaved off, which is later catabolized to pyruvate and ammonia.
5. Uptake and Proteolysis of Thyroglobulin:
Thyroid follicular cells then pinocytoze the colloid from follicular lumen. The droplets coalesce with lysosomes. Lysosomal secretion contains proteases, glycoside hydrolyase and endo-peptidases. Lysosomal secretions hydrolyze thyroglobulin to release T4, DIT and MIT.
T4 and T3 pass to blood by facilitated diffusion through follicular cell membrane but DIT and MIT de-iodinated by microsomal deiodinase. The liberated iodine is reused for iodination of tyrosine (Fig. 6.5 and Fig. 6.6).
Transport of T3 and T4 Hormones:
Only small amounts of T3 and T4 (less than 1% of the T3 and less than 0.1% of the T4) are transported in free state in blood plasma. The major amounts are transported in binding with plasma protein. T4 remains bind with thyroxine binding globulin (TBG), thyroxine binding pre-albumin (TBPA) and serum albumin. T3 is transported through TBG only. Both T3 and T4 are carried through blood to tissues. Most T3 (about 80%) in blood however, comes from de-iodination of T4 in peripheral tissues and not directly from the thyroid gland itself.
Catabolism of T3 and T4 Hormones:
The liver and kidneys are the chief organs concerned in the catabolism of thyroid hormones. In the liver, maximum amounts are de-iodinated by enzyme deiodinase and then excreted in the bile and urine as glucuronates, sulfates and methyl conjugates. Both free and conjugated forms of thyroxine are excreted in small amounts through the kidneys. In case of T3, 80% is de-iodinated and 20% is excreted through faeces.
Control of Secretion of T3 and T4 Hormones:
Ts and T4 synthesis and secretion are chiefly controlled by coordination of hypothalamus and adenohypophysis. On stimulation TSH- RH is secreted from hypothalamus and then stimulates adenohypophysis to secrete TSH which in turn stimulates thyroid follicular cells for secretion of T3 and T4.
The secretion of TSH-RH is inhibited by hyper secretion of TSH by negative feedback mechanism. The excess secretion of T3 and T4 control the secretion of TSH by negative feedback mechanism (Fig. 6.7).
Certain anti-thyroid drugs like thiourea, thiouracil etc. inhibit the thyroxine synthesis.