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 epithelia l polarity: secretion of thyroglobulin (Tg) to the apical lumen, uptak e of iodide for Tg iodination, and the manufacture of thyroid hormone for delivery to the bloodstream. In this report we examine Tg processi ng by thyroid epithelial monolayers cultured on porous filters. Basola teral I-125 uptake resulted in thyrotropin-dependent radiolabeling of Tg in cells and apical medium. Polarized thyrocytes iodinated exogenou s gamma globulins (IgG), demonstrating labeling in the apical extracel lular space. Apical catalase addition inhibited the appearance of apic al, [I-125]IgG and [I-125]Tg, but had no effect on cell-associated [I- 125]Tg, indicating additional iodination of Tg in an intracellular com partment. A similar conclusion was drawn from radioiodination experime nts at 20 degrees C. Intracellular iodination was selective for Tg for ms receiving prior Golgi carbohydrate modifications. During a 2-h chas e, [I-125]Tg was exported from cells to apical medium, while modest am ounts of thyroxine were secreted with a majority to the basolateral me dium. Neither radioiodination at 20 degrees C nor apical catalase addi tion blocked formation or secretion of [I-125]thyroxine during the cha se. Thus in filter-grown thyroid epithelial cells, prior to apical ext racellular iodination, intracellular iodination of Tg begins the proce ss leading to formation of thyroxine.