Apoptosis during goitre involution - the role of Bcl-2

Goitrogenesis is accompanied by hyperplasia and hypertrophy and involves ti ssue remodelling and angiogenesis. During the involution of the goitre ther e must be removal of this increased thyroid volume, in addition to further remodelling, which may involve apoptosis. We investigated apoptosis in the involuting rat thyroid using male Fisher rats that were on a goitrogenic re gimen for 14 days and then returned to a normal diet. Thyroid weights incre ased fourfold with the goitrogenic regimen. During involution, the largest decrease in weight was between day 2 and day 4 after withdrawal of treatmen t. After 34 days of involution, the thyroid weight plateaued, but had not r eturned to control values. High levels of Bcl-2 immunoreactivity were obser ved in normal and goitrous rat thyroids. These high levels were significant ly reduced at 2 days of involution, after which high levels of Bcl-2 immuno reactivity returned. In situ end-labelling of apoptotic cells showed that t here was an increase in the number of cells undergoing DNA fragmentation du ring goitrogenesis (1.0 +/- 0.8 cells/100 cells, n=9) compared with control s, in which no positive staining was observed. After 2 days of goitrogen wi thdrawal, there was a further four-fold increase in the number of in situ e nd-labelled cells (day 16: 4.1 +/- 1.7, n=9). Numbers of positive cells ret urned to low levels after 4 days of involution (day 18: 0.3 +/- 0.8, n=9). Using antiserum to apoptosis-specific protein, we found increased immunorea ctivity during goitrogenesis and after 2 days of involution that was locali sed predominantly with the stromal and vascular tissue at both time points. The data show that rapid downregulation of Bcl-2 accompanies thyroid invol ution, which involves increased levels of apoptosis within the stromal comp artment.