The Inhibitory Action of Excessive Iodide Upon the Synthesis of Diiodotyrosine and of Thyroxine in the Thyroid Gland of the Normal Rat1

Both chemical (Harington, 1944, 1945; von Mutzenbecher, 1939; Block, 1940, Reineke and Turner, 1942) and biochemical evidence (Perlman et al., 1941; Morton et al., 1943; Taurog et al., 1947; Leblond, 1942) has shown that at least 2 steps are involved in the synthesis of thy.roxine: 1) iodination of tyrosine to form diiodotyrosine and 2) coupling of 2 diiodotyrosine molecules to form thyroxine. While the exact nature of step 1 is not well understood, it is apparent that the iodide reaching the thyroid gland from the blood must be oxidized either to I2 or to HIO before it can be incorporated into the phenolic group of tyrosine. The subsequent coupling of 2 diiodotyrosine molecules is believed by both Harington (1945) and Johnson and Tewkesbury (1942) to be an oxidative reaction in which the oxidized form of iodide (I2 or HIO) plays a significant role.