EXTRATHYROIDAL RELEASE OF THYROID-HORMONES FROM THYROGLOBULIN BY J774 MOUSE MACROPHAGES

Thyroglobulin appears in the circulation of vertebrates at species-specific concentrations. We have observed that the clearance of thyroglobulin from the circulation occurs in the liver by macrophages. Here we show that the thyroid hormones T-3 and T-4 were released by incubation of mouse macrophages (J774) with thyroglobulin. Thyroid hormone release was a fast process, with an initial rate of similar to 20 pmol T-4/mg per min and similar to 0.6 pmol T-3/mg per min, indicating that macrophages preferentially release T-4. The bulk of released thyroid hormones appeared after 5 min of incubation of macrophages with thyroglobulin, whereas degradation of the protein was detectable only after several hours. During internalization of thyroglobulin, endocytic vesicles and endosomes were reached at 5 min and lysosomes at 60 min. T-4 release started extracellularly by secreted proteases and continued along the endocytic pathway of thyroglobulin, whereas T-3 release occurred mainly intracellularly when thyroglobulin had reached the lysosomes. This shows that the release of both hormones occurred at distinct cellular sites. Our in vitro observations suggest that macrophages in situ represent an extrathyroidal source for thyroid hormones from circulating thyroglobulin.