Enhanced release of T3 and rT3 compared to T4 from thyroglobulin during autolysis of dog thyroid homogenate

Previous studies on the secretion of thyroxine (T4), 3,5,3'-triiodothyronine (T3), and 3,3',5'-triiodothyronine (rT3) from perfused dog thyroids have indicated that a differential rate of secretion of various iodothyronines may take place. The aim of the present study was to evaluate whether the proteolysis of thyroglobulin taking place during secretion could be involved in this phenomenon. Homogenate from the same dog thyroid was incubated either at pH 3.6 for 18 h without added protease or with pronase at pH 8.4 for 18 h. Iodothyronines were measured radioimmunologically in ethanol extracts of the hydrolysates. No significant deiodination of T4 to T3 and rT3 took place during incubation. During acid autolysis 17.5 +/- 3.5% (mean +/- SE, n = 5) of the T4 found after pronase hydrolysis was liberated, while 31.6 +/- 4.8% of the T3 and 21.2 +/- 4.2% of the rT3 were liberated (both values were significantly higher than that found for T4). Since iodothyronines in thyroglobulin are released nearly quantitatively during pronase hydrolysis, the results indicate that thyroid proteases acting at acid pH, liberates T3 and rT3 more easily than T4 from thyroglobulin. This could be the mechanism behind the relatively high secretion of T3 and rT3 observed during acceleration of secretion from perfused thyroid lobes, and the relatively high secretion of T4 observed during deceleration of secretion.