[Biosynthesis of thyroid hormones].

Several problems are involved in the studies on the biosynthesis of thyroid hormones : 1) How are iodine atoms incorporated into a thyroglobulin (TG) molecule ? 2) How is the matured TG molecule built up? 3) how are carbohydrates incorporated in a TG molecule? 4) How are amino acids assembled to make up TG polypeptides? 5) How is TG hydrolyzed to produce T3 and T4 ? Recent progresses concerning the first four questions are briefly summarized and discussed below. Tarutani's recent finding of non-iodinated TG from goitrogen-treated pigs confirmed that the most of iodine atoms are incorporated into TG after the formation of molecules with M.W. of 660,000. Micro villi or adjacent region was reported as a site of the iodination from biochemical and electron microscopic studies. With regard to the final step of the iodination, two DIT residues in TG polypeptides were suggested to be direct precursors of thyroxine on the basis of the comparison of chemically-iodinated and enzymatically iodinated TG with naturally existing TG. Studies on carbohydrate incorporation into TG were progressed by Spiro and Bouchilloux et. al. They concluded that carbohydrates are incorporated at microsomal membranes, presumablly at rough sufaced E.R, into TG polypeptides after the completion of peptide formation. Enzymological studies on the process also have been taken place by Spiro. The biochemical mechanism of thyroxine formation, the acutal process of molecular maturation in vivo, the roles of carbohydrate for the building of the molecule and for the biolo[gical functions of the molecule are some of the points remaining to be elucidated. The in vitro studies on protein synthesis in the thyroid have been done by the author as well as American and French groups. Although Nunez reported that amino acids are incorporated into the same protein fraction as matured TG in his polysomal system, all others' results were not consistent with his conclusion and confirmed the microsomal synthesis of matured TG and the inability of polysomes in terms of production of the matured TG. In the author's studies a. new polysomal system was reconstructed which consisted of pig thyroid polysomes, liver t-RNA charged with labeled and unlabeled amino acids and liver cell sap as an enzyme mixture supplemented with the amino acid activating system. For the first 10 min. of incubation did the reaction proceed rapidly and slowed down after that period. An average length of the newly synthesized portion of the pep'tides in non-dialy-s able proteins which were released from polysomes by the treatment with RNase and EDTA (0.1 M) or with SDS (0.1 %), corresponded to 20 amino acid residues. Amino acid incorporation increased with the concentration of polysomes showing the dependency of the