Fas-mediated apoptosis is inhibited by TSH and iodine in moderate concentrations in primary human thyrocytes in vitro

Programmed cell death (apoptosis) can be found in normal thyroid tissue and in Various diseases affecting the thyroid gland. The Fas/Fas ligand (FasL) system is involved in the induction of apoptosis in human thyrocytes. Cros s-linking the Fas receptor with its own ligand or with an antibody capable of oligomerizing with the receptor induces programmed cell death. We invest igated the role of Fas-induced apoptosis in primary human thyrocytes in vit ro. Cell cultures of normal human thyrocytes were prepared from specimens o btained during surgery for uninodular goiter. Apoptosis was induced by incu bation of the cells with a monoclonal IgM anti-fas antibody. The presence o f apoptosis was determined by FAGS analysis of FITC-labelled annexin V bind ing combined with dye exclusion of propidium iodide. We found a significant rate of Fas-induced apoptosis in normal thyrocytes after activation with a monoclonal anti-fas antibody. TSH was able to inhibit Fas-mediated apoptos is in a dose-dependent manner. This effect was more pronounced when thyrocy tes were incubated in the presence of interferon-gamma. Low concentrations of iodine were able to inhibit apoptosis, while high concentrations of iodi ne increased the rate of Fas-induced apoptosis. Our results show that Fas-m ediated apoptosis is inducible in normal human thyrocytes in vitro and is i nfluenced by TSH and iodine. The Fas/FasL system may play an important role in the regulation of cell number within the thyroid gland, and may be invo lved in the processes leading to goiter in iodine deficiency.