CELL-PROLIFERATION AND APOPTOSIS OF THYROID FOLLICULAR CELLS ARE INVOLVED IN THE INVOLUTION OF EXPERIMENTAL NONTUMORAL HYPERPLASTIC GOITER

To assess the involvement of cellular inhibition and the appearance of apoptosis in regression of the hyperplastic thyroid gland towards nor mality, an experimental design was used to elicit non-toxic goiter by inducing hyperplastic goiter in rats by treatment with methimazole. We performed a morphological and PCNA immunocytochemical study together with in situ end labelling with bromodeoxyuridine in thyroid glands of rats receiving methimazole in their drinking water over 21 days after which they were allowed a recovery period of 0, 12, 24, 36, 48 and 72 h and 7, 14, 21 and 44 days. Serum T-3 and T-4 levels were found to b e very low in the methimazole-treated animals although they increased after the goitrogenic compound had been withdrawn. Inhibition of cell proliferation and the burst of apoptosis play important roles in the r egression of hyperplastic goiter in rats. Cell. proliferation, which w as strongly stimulated during goiter, fell significantly at 24 h, ther eafter decreasing gradually as the recovery period progressed. Isolate d cases of thyrocyte necrosis were observed ultrastructurally. Light a nd transmission electron microscopy revealed the existence of thyroid apoptosis with respect to the development of the study over time. Most apoptotic thyrocytes became detached from the follicular epithelium a nd later underwent cellular degeneration in the follicular lumen. The remaining apoptotic cells retracted their cytoplasm, lost contact with the follicular lumen and became located at the base of the follicles. The percentage of apoptosis showed that during the first week of thyr oid involution apoptosis was already present but with low percentages while maximum values were attained at 21 days of survival. Our results suggest that, in the rat, during the return of thyroid follicular cel ls to normality after methimazole-induced hyperplastic goiter a balanc e arises between proliferation and cell death and that this balance is due to the inhibition of cellular proliferation and, secondarily, to the appearance of apoptosis, which becomes particularly evident toward s the end of the first week after withdrawing the goitrogenic agent.