Extrathyroidal release of thyroid hormones from thyroglobulin by J774 mouse macrophages.

Abstract

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 T3 and T4 were released by incubation of mouse macrophages (J774) with thyroglobulin. Thyroid hormone release was a fast process, with an initial rate of -20 pmol T4/mg per min and 0.6 pmolT3/mg per min, indicating that macrophages preferentially release T4. The bulk of released thyroid hormones appeared after 5 min ofincubation ofmacrophages with thyroglobulin, whereas degradation of the protein was detectable only after several hours. During internalization ofthyroglobulin, endocytic vesicles and endosomes were reached at 5 min and lysosomes at 60 min. T4 release started extracellularly by secreted proteases and continued along the endocytic pathway of thyroglobulin, whereas T3 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. (J. Clin. Invest. 1994Invest. .93:1388Invest. -1396

Amiodarone induces a different pattern of ultrastructural change in the thyroid to iodine excess alone in both the BB/W rat and the Wistar rat

“…The accumulation of secondary lysosomes has been previously described in the thyroid of rats with a high iodine intake (five times the present dose and longer exposure to the iodine), and certainly these were evident in both AMD-and NaItreated rats (30). This finding is often explained by the accumulation of highly iodinated thyroglobulin which is resistant to proteolytic degradation (33,37,38). An increased number of lysosomes is also a well reported finding of AMD-induced ultrastructural change in other tissues (11,39,40).…”

Identification of thyroid hormone residues on serum thyroglobulin: a clue to the source of circulating thyroglobulin in thyroid diseases

“…The group of Herzog (23,24) recently reported that macrophages in culture are capable of releasing T4 and T3 from Tg, a process requiring the internalization and then the proteolytic processing of Tg. Furthermore, these authors suggest that T3 and T4 produced by Kupffer cells of the liver could directly act on neighboring hepatocytes.…”

The type‐1 repeats of thyroglobulin regulate thyroglobulin degradation and T3, T4 release in thyrocytes

“…The thyroid hormone residues are released by early and limited alteration of the Tg structure [3]. Intensive Tg degradation is a delayed process, requiring several hours [4]. In spite of numerous reports on Tg proteolytic attacks by thyroid proteases [5][6][7][8][9], the physiological mechanisms for selective hormone release and sequential processing remain unclear.…”