Involution of rat iodoprive hyperplastic goiter: Effect of iodide administration on thyroid function and lysosomal properties

Abstract

Involution of iodoprive hyperplastic goiters was induced by physiological iodide supplementation (5 μg/rat, ip, 1, 3, 6, and 24 h before the animals were killed and 10 μg in water/ rat·day for 2,4, 9, and 21 days). During goiter regression, thyroid secretion and biochemical properties of the lysosomes were closely connected with the modifications in cellular functions. Involution proceeded in three successive stages. In the first phase (first day of treatment), endocytosis and the hydrolysis of newly synthesized thyroglobulin (Tgb) were maximal. A transient hypersecretion of T3 and a progressive inhibition of TSH release were observed. Soluble Tgb did not accumulate. Lysosomes had a reduced stability. In the second stage (first to fourth days of treatment), cellular hypertrophy was progressively abolished. TSH levels and thyroid hormone secretion were normal. Tgb accumulated. The RNA content of the glands regressed rapidly. At this time, lysosomal destabilization was reversed, and lysosomes became highly stable, suggesting that large autolysosomes were not involved in the regression of the cellular volume. The total activities of four acid hydrolases began to increase, and the lysosomal membrane was progressively more susceptible to acid autolysis. After day 4 of treatment, a high cell loss took place. During this third stage, lysosomal properties were similar to those observed in normal animals. The total activities of the lysosomal enzymes increased gradually, up to supranormal values. It was suggested that this increased activity, which could be under thyroid hormone control, corresponded to new enzyme molecules included in primary lysosomes and caused irreversible and deadly lesions to thyroid cells.