Role of Apoptosis of Thyrocytes in a Rat Model of Goiter. A Possible Involvement of Fas System¹

Abstract

Apoptosis, a physiological process of cell death, may modulate the mass of the thyroid gland. We investigated the role of apoptosis and the possible involvement of Fas/Fas ligand (FasL) system in apoptosis during 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 induce goiter. Rats with goiter were then fed a high iodine diet to study the phase of involution. We examined the presence of apoptosis by electron microscopy (EM) and terminal deoxy-UTP nick end labeling (TUNEL). We also investigated the association between Fas and FasL expression and thyrocyte apoptosis using immunohistochemistry and Western blotting. To evaluate the proliferation of thyrocytes, proliferating cell nuclear antigen was examined immunohistochemically. The number of apoptotic cells increased during goiter formation and the early stage of involution, which were also associated with increased number of Fas-positive thyrocytes, and some of these cells contained TUNEL-positive nuclei. However, the expression of FasL was almost constant throughout the experiment. Proliferating cell nuclear antigen/TUNEL ratio markedly increased during goiter formation but decreased particularly during the late stage of goiter involution. Our results indicate that apoptosis of thyrocytes is a main factor of cell loss during goiter formation and involution and suggest that the Fas/FasL system is involved in the induction of apoptosis of these cells. Moreover, the delicate balance between apoptosis and cell proliferation may play an important role in the control of thyroid gland mass.

Cell necrosis and apoptosis are differentially regulated during goitre development and iodine-induced involution

“…Apoptosis, as assessed by measurement of TUNELpositive cells, increased during goitre formation in experimental rats (Tamura et al 1998). The reliability of this method is questionable when apoptosis is to be compared with necrosis.…”

“…Cell death plays a central role in regulating the thyroid cell mass, especially during the goitre involution induced by iodine or by thyroid hormones (Wollman et al 1968, Denef et al 1981, Rognoni et al 1987. In addition, a balance between cell death and proliferation has also been reported during goitre development itself (Tamura et al 1998). Indeed, stimulated thyrocytes could be considered as being under oxidative stress: high TSH plasma levels activate H 2 O 2 production (for review see Dumont et al 1992) which largely exceeds its consumption by thyroid hormone synthesis (Corvilain et al 1991).…”

“…More recently, apoptosis has been reported during goitre formation in rats, with a further increase during the early stage of goitre involution with normal (Patel et al 2000) or high iodine doses (Tamura et al 1998), but the respective roles of apoptosis and necrosis were not quantified.…”

Inflammatory Cytokine Regulation of Fas-mediated Apoptosis in Thyroid Follicular Cells

“…Apoptosis is one mechanism by which cytotoxic T lymphocytes can destroy thyrocytes in thyroiditis, which in turn may lead to hypothyroidism (6,8). In contrast, the suppression of apoptosis may contribute to thyroid proliferative diseases including goiter, cancer, and Graves' disease (7,8). However, little is known about the mechanisms and regulation of apoptotic signaling in thyroid cells.…”

TRAIL Death Pathway Expression and Induction in Thyroid Follicular Cells

“…Morphological changes indicative of PCD have been observed in normal thyroid glands and appear at increased frequency in thyroid tissue affected by chronic autoimmune thyroiditis (7)(8)(9). PCD is also a mechanism by which cytotoxic T lymphocytes can destroy thyrocytes, which in turn may lead to hypothyroidism (7,8).…”