The role of iodination in the formation of hormone-rich peptides from thyroglobulin.

Reduced thyroglobulins from several animal species contain hormone-rich iodopeptides of 20,000-26,000 and 15,000-18,000 daltons. The present study has investigated the role of iodination in their production. Experimental approaches have included: iodination in vitro of thyroglobulin from rabbit thyroid slices incubated with [3H]leucine and subsequent analysis of 3H distribution by gel electrophoresis; iodination in vitro of low iodine thyroglobulin from a human goiter, followed by isolation of the major iodopeptides and quantitation of their peptide content; and injection of iodine-deficient rats with Na125I and assessment of the distribution of isotope among the iodopeptides at successive time intervals. From these experiments the following general pattern has emerged: 1) at low levels of iodine (less than 5 atoms/molecule of thyroglobulin) in vitro or at short time intervals after iodine administration in vivo (less than 4 h), the principal iodinated component of reduced thyroglobulin is a approximately 230,000-dalton peptide; 2) with moderate increases in iodine (5-40 atoms/molecule) or longer time intervals after administration (greater than or equal to 4 h) there is less of the 230,000-dalton iodopeptide, and an iodothyronine-rich approximately 20,000- to 26,000-dalton iodopeptide appears; 3) at higher levels of iodine (greater than 40 atoms/molecule) the amount of approximately 230,000-dalton iodopeptide decreases further, the amount of 20,000- to 26,000-dalton iodopeptides may decrease, and an iodothyronine-rich 15,000- to 18,000-dalton peptide appears. Progressive iodination gives the same changes in distribution of peptide material among these iodopeptides as it does in iodine distribution, and the changes seen with iodination in vitro are similar to those occurring over time in vivo. We conclude that during the process of iodination discrete peptide bonds of thyroglobulin are cleaved to produce the hormone-rich iodopeptides. This is probably a normal part of thyroglobulin maturation in vivo and may be a necessary event preceding hormone formation.