Inhibition of thyroid iodine uptake and organification in rats treated with kojic acid

In order to elucidate the mechanisms of reduction of serum thyroid hormones caused by continuous administration of kojic acid (KA) and its thyroid tum or-promotion effects, male F344 rats were given pulverized basal diet conta ining 0.008%, 0.03%, 0.125%, 0.5%, or 2% KA for 4 weeks. As an untreated co ntrol group, additional rats were given basal diet alone for the same perio d. The thyroid I-125 uptake was significantly decreased in the groups recei ving 0.03% or more. In addition, significant reduction of organic formation of iodine and serum T3 and T4 levels were observed in the 2% KA group alon g with pronounced elevation of serum (TSH). Both absolute and relative thyr oid weights were significantly increased in the groups receiving 0.5% of KA or more. Histopathologically, decreased colloid in the thyroid follicles a nd follicular cell hypertrophy in the thyroid were apparent at high inciden ces in the groups given 0.03% or more. In addition, thyroid capsular fibros is was evident in all rats of the 2% KA group. In quantitative morphometric al analysis, the ratio of the area of follicular epithelial cells to the ar ea of colloids was significantly increased in the groups given 0.03% KA or more. The results suggest that KA alteration of thyroid-related hormone lev els in the 2% KA group are due to inhibition of iodide uptake and iodine or ganification in the thyroid, with tumor-promoting effects on development of thyroid proliferative lesions, probably secondary to prolonged serum TSH s timulation resulting from negative feedback through the pituitary-thyroid a xis.