Non-thyroglobulin Iodine of the Thyroid Gland

Thyroxine in the thyroid gland is considered to be firmly built into the protein molecule, thyroglobulin (1). Only after the gland is hydrolyzed with fairly strong alkali does its thyroxine become readily extractable with butyl alcohol. The iodine which circulates in plasma, on the other hand, can be almost completely extracted with butyl alcohol without previous hydrolysis (2). Considerable evidence now supports the view that the circulating thyroid hormone is thyroxine loosely bound to plasma protein (2-5). The bond between thyroxine and the protein is readily broken when plasma is extracted with butyl alcohol at room temperature. If the hormone delivered to the circulation by the gland is indeed free thyroxine, the presence of at least a small amount of free thyroxine in the thyroid gland may be expected. Leblond, Gross, and coworkers following this line of reasoning, have used the methods of isotope dilution and filter paper chromatography to demonstrate the presence of free thyroxine in unhydrolyzed thyroid tissue (5, 6). The methods used by these workers did not, however, reveal the actual quantity of free thyroxine present in the gland, although they were able to show that the free thyroxine concentration of the gland was much greater than that of the plasma. With the aid of filter paper partition chromatography and a sensitive method for measuring chemical iodine, we have obtained values for the actual quantities of free thyroxine and other iodine-containing compounds in the thyroid gland. It is shown here that free thyroxine comprises only about 0.5 per cent of the total iodine of rat thyroid, and that the gland contains about the same amount of free diiodotyrosine. Free monoiodotyrosine, on the other hand, is practically absent. The results of experiments dealing with the metabolic significance of the small amounts of free thyroxine in the gland are also reported here.