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

J. Mutaku
2002 Journal of Endocrinology  
Necrosis and apoptosis coexist in the thyroid during goitre development and involution, but little is known about their respective causes. To test the possible role of free radicals, we analysed separately necrosis and apoptosis in male Wistar rats with depressed or normal antioxidant protection. Vitamin E-deficient and -sufficient rats were made goitrous with perchlorate in drinking water; involution was induced by repeated injection of NaI, without or with methimazole. Increase of thyroid
more » ... ease of thyroid malondialdehyde concentration and decrease of glutathione peroxidase activity confirmed the depressed antioxidant protection in vitamin E-deficient rats. Plasma thyroxine and TSH levels were not modified. Necrosis (swollen cells) and apoptosis (pyknotic cells) were quantified on histological sections. In vitamin E-sufficient rats, dead cells were very rare in control thyroids, increased 3-fold in goitre and still further during involution. Necrotic epithelial cells predominated in the goitre and their number declined after iodide supplementation, without or with methimazole. In contrast, the number of apoptotic cells and the caspase-3 activity were increased in goitre and further increased after involution, with twothirds of pyknotic cells being observed in the interstitium. Apoptosis was prevented by methimazole. Vitamin E deficiency significantly increased total cell death and epithelial cell necrosis and induced the occurrence of much cell debris in the follicular lumen during involution, with no modification of the apoptotic reaction. These results show that the type of cell death is differentially regulated during goitre development and involution: necrosis is related to the oxidative status of the cells, while apoptosis comes with iodine-induced involution. Downloaded from Bioscientifica.com at 03/07/2020 04:17:56PM via free access goitrous rat; bar=5 m. Two necrotic cells (arrows) are visible in the epithelial wall; nuclei are pale and cytoplasms are swollen and vacuolar. Apoptotic bodies correspond to fragmented pyknotic nuclei (arrowhead). (B-D) NaI-treated E goitrous rats; bar=1 m. Necrosis corresponds to organelle swelling and disruption (C). Apoptotic bodies are endocytosed in the interstitium (B). Note that cell debris is often very dense in the follicular lumen (D). Necrosis and apoptosis in goitre and involution · J F MUTAKU and others 381 Figure 3 Quantification of various aspects of total dead cells (A) and epithelial death type (B). E + and E rats were either untreated (control group), made goitrous by drinking perchlorate (goitre group), further injected with NaI alone (involution group) or with MMI (involution+MMI group). There were 100 cells/field. Means S.D., n=5. Results of statistical analysis were as follows. Total number of dead cells: vitamin effect: significant for P<0·001; treatment effect: P<0·001; interaction: P<0·05. Number of interstitial dead cells: vitamin effect: ns; treatment effect: P<0·001; interaction: ns. Number of epithelial dead cells: vitamin effect: P<0·001; treatment effect: P<0·001; interaction: ns. Epithelial necrotic cells: vitamin effect: P<0·01; treatment effect: P<0·001; interaction: ns. Epithelial apoptotic cells: vitamin effect: ns; treatment effect: P<0·05; interaction: ns. J F MUTAKU and others · Necrosis and apoptosis in goitre and involution 382
doi:10.1677/joe.0.1720375 pmid:11834455 fatcat:v4m5ebjgiva3dkwbyvwilns5su