Intracellular iodination of thyroglobulin in filter-polarized thyrocytes leads to the synthesis and basolateral secretion of thyroid hormone.
Thyroid follicles perform several functions that depend upon epithelial polarity: secretion of thyroglobulin (Tg) to the apical lumen, uptake of iodide for Tg iodination, and the manufacture of thyroid hormone for delivery to the bloodstream. In this report we examine Tg processing by thyroid epithelial monolayers cultured on porous filters. Basolateral 125I uptake resulted in thyrotropin-dependent radiolabeling of Tg in cells and apical medium. Polarized thyrocytes iodinated exogenous gamma globulins (IgG), demonstrating labeling in the apical extracellular space. Apical catalase addition inhibited the appearance of apical [125I]IgG and [125I]Tg, but had no effect on cell-associated [125I]Tg, indicating additional iodination of Tg in an intracellular compartment. A similar conclusion was drawn from radioiodination experiments at 20 degrees C. Intracellular iodination was selective for Tg forms receiving prior Golgi carbohydrate modifications. During a 2-h chase, [125I]Tg was exported from cells to apical medium, while modest amounts of thyroxine were secreted with a majority to the basolateral medium. Neither radioiodination at 20 degrees C nor apical catalase addition blocked formation or secretion of [125I]thyroxine during the chase. Thus in filter-grown thyroid epithelial cells, prior to apical extracellular iodination, intracellular iodination of Tg begins the process leading to formation of thyroxine.
Kuliawat
R
R
Division of Endocrinology, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts 02215.
Arvan
P
P
D000818:Animals; D001692:Biological Transport; D002374:Catalase / Q000494:pharmacology; D002455:Cell Division; D002478:Cells, Cultured; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D007454:Iodides / Q000378:metabolism*; D007457:Iodine Radioisotopes; D007700:Kinetics; D013552:Swine; D013696:Temperature; D013954:Thyroglobulin / Q000378:metabolism*; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology; D013974:Thyroxine / Q000096:biosynthesis* / Q000378:metabolism
D007074:Immunoglobulin G; D007454:Iodides; D007457:Iodine Radioisotopes; D013972:Thyrotropin; D013954:Thyroglobulin; D002374:Catalase; D013974:Thyroxine