Differences between circulating and tissue thyroglobulin in rats

The mechanism whereby thyroglobulin (TG) reaches the circulation can involve either the release of newly synthesized TG or the release of colloid-stored TG from the thyroid gland. To distinguish between these possibilities, we have compared the properties of circulating and glandular TG in normal and thyroidectomized thyroid tumor-bearing rats. Circulating TG had the properties of poorly iodinated molecules; it was more susceptible to dissociation into subunits and had a lower density, the latter determined by equilibrium centrifugation in concentrated RbCl. The density of circulating TG was the same as that of glandular TG from propylthiouracil-treated rats, suggesting that circulating TG was nearly or completely devoid of iodine. Circulating TG bound to Concanavalin A-Sepharose and had a normal MCR, indicating that mannose was present and galactose was not in terminal positions, both properties of glandular TG. Since previous studies suggest that these properties cannot arise from differential clearance of TG molecules in the periphery, these data suggest that the TG in the circulation may arise from the direct release of poorly iodinated newly synthesized TG from the thyroid.