No abstract

When grown in the presence of thyrotropin, dog thyroid cells in culture from follicle-like structures, take up labeled iodide, and iodinate macromolecular components in the cell. When grown in the absence of thyrotropin, dog thyroid cells in culture form a monolayer, take up only 6% of the iodide of follicular cells, and do not iodinate macromolelcular components in the cell. The iodide uptake in monolayer cells does, however, reflect an incorporation process unique to thyroid cells because hepatocytes and fibroblasts do not have the capacity of the monolayer cells to take up iodide. Thyrotropin stimulation of monolayer cells for a prolonged period (3-8 days) causes the cAMP levels of these cells to return to levels identical to those in follicular cells. The increased cAMP levels are not due to the induction of an adenylate cyclase enzyme, because homogenates of monolayer cells have a thyrotropin-stimulable adenylate cyclase activity. The low level of cAMP, thus, seems to be a problem of receptor coupling to the adenylate cyclase enzyme. The return of cAMP to normal levels is accompanied by an increase in iodide uptake and by macromolecular organification; the return of cAMP levels to normal values is not accompanied by follicular development. The majority (75%) of the iodinated macromolecular product accumulated by follicular thyroid cells, by monolayer thyroid cells stimulated with thyrotropin for a prolonged period, or by thyroid cells treated with dibutyryl cAMP from the onset of culture has the characteristics of 19 S thyroglobulin. The remainder appears to be low mol wt material which may be thyroglobulin-related i.e., be either precursor or biodegraded material.

This study describes an assay for the detection of cytotoxicity for thyroid cells in serum of patients with autoimmune thyroiditis. Quantitative measurement may be performed by DNA or [3H] leucine incorporation determinations. The cytotoxic effect is localized in the gamma-globulin fraction, and is complement-mediated. It is thyroid specific i.e. it is not observed with fibroblasts and patients with other autoimmune diseases (patients with lupus erythematosis or glomerulonephritis) do not have cytotoxic antibodies directed against thyroid cells. The thyroid cytotoxicity is related to the presence of antimicrosomal antibodies and the effect of circulating antibodies is inhibited by human thyroid peroxidase. These results strengthen the possible implication of circulating antithyroid peroxidase antibodies in thyroid damage observed in autoimmune thyroiditis.