Goitrogen-induced thyroid growth in the rat: a quantitative morphometric study

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Abstract
This study was designed to investigate quantitatively the changes in thyroid morphology which accompany goitrogen-induced thyroid growth in the rat and to relate these changes to the level of serum thyrotrophin (TSH). Animals treated with the goitrogen aminotriazole were killed, together with controls, at frequent intervals up to 153 days. A carefully controlled perfusion-fixation technique was employed, together with plastic embedding, to ensure optimal preservation of in-vivo morphology, and attention was paid to stereological principles in the methods of tissue sampling. Morphometric analysis was carried out by 'point-counting' to obtain the proportion of thyroid volume occupied by each of four components: epithelial cells, follicular lumen, blood vessels and non-vascular stroma. Total thyroid weight was measured, from which the total volumes of each component were calculated. Serum TSH was measured by radioimmunoassay. Goitrogen treatment led to a rapid rise in the level of serum TSH, reaching a sustained fivefold maximum by day 82. Total thyroid weight increased to a 12-fold plateau after 116 days. There was a rapid change during the first week in the proportional volumes of component tissues; a rise in the epithelial cell and blood vessel components being accompanied by a corresponding fall in follicular lumen and non-vascular stroma. Total epithelial cell volume rose in parallel with thyroid weight to reach a 16-fold maximum. There was a more marked (34-fold) increase in vascular volume and there were smaller increases in the other two components. No significant growth occurred after 116 days. The results show that goitrogen-induced changes in thyroid morphology are complete at submaximal levels of TSH stimulation and that growth then proceeds by a proportional increase in all components. The morphological changes persist, but growth eventually ceases, despite a sustained rise in the level of serum TSH, thus pointing to the existence in the thyroid of a growth-limiting control mechanism.