ROLE OF APOPTOSIS OF THYROCYTES IN A RAT MODEL OF GOITER - A POSSIBLEINVOLVEMENT OF FAS SYSTEM

Apoptosis, a physiological process of cell death, may modulate the mas s of the thyroid gland. We investigated the role of apoptosis and the possible involvement of Fas/Fas ligand (FasL) system in apoptosis duri ng goiter formation and involution in a rat model of goiter. Rats were fed a low iodine diet and a goitrogen, 6-propyl-2-thiouracil, to indu ce goiter. Rats with goiter were then fed a high iodine diet to study the: phase of involution. We examined the presence of apoptosis by ele ctron microscopy (EM) and terminal deoxy-UTP nick end labeling (TUNEL) . We also investigated the association between Fas and Fast expression and thyrocyte apoptosis using immunohistochemistry and Western blotti ng. To evaluate the proliferation of thyrocytes, proliferating cell nu clear antigen was examined immunohistochemically. The number of apopto tic cells increased during goiter formation and the early stage of inv olution, which were also associated with increased number of Fas-posit ive thyrocytes, and some of these cells contained TUNEL-positive nucle i. However, the expression of Fast was almost constant throughout the experiment. Proliferating cell nuclear antigen/TUNEL ratio markedly in creased during goiter formation but decreased particularly during the late stage of goiter involution. Our results indicate that apoptosis o f thyrocytes is a main factor of cell loss during goiter formation and involution and suggest that the Fas/FasL system is involved in the in duction of apoptosis of these cells. Moreover, the delicate balance be tween apoptosis and cell proliferation may play an important role in t he control of thyroid gland mass.