Changes in thyroid function during development of thyroid hyperplasia induced by kojic acid in F344 rats

To clarify the mechanism of tumorigenesis by kojic acid (KA), dose and time dependence of iodine uptake in the thyroid gland and serum thyroid stimula ting hormone (TSH) and thyroid hormone levels were investigated in F344 rat s fed a diet containing 2% KA, After 4 weeks, thyroid hyperplasia was appar ent in males, associated with a decrease in I-125 Uptake into the thyroid g land to only 3% of that in controls. The serum triiodothyronine (T-3) and t hyroxine (T-4) levels dropped to 0.36 ng/ml, 1.7 mu g/dl from the initial v alues of 0.61 ng/ml, 4.0 mu g/dl and TSH increased seven times to 15 ng/ml, In females, the effects on thyroid weight and I-125 uptake were less promi nent, although the changes in serum T-3, T-4 and TSH levels were similar to those in males. Time-dependent changes in serum T-3, T-4 and TSH levels co rrelated with the inhibition of iodine uptake in the thyroid, Inhibition of organic iodine formation was only observed after 3 weeks treatment. On ret urn to the control diet, normal serum T-3, T-4 and TSH levels became eviden t within 48 h in both sexes. These data suggest that KA interrupts thyroid function, primarily by inhibiting iodine intake, consequently causing a dec rease in serum T-3 and T-4. Increased TSH from the pituitary gland in turn stimulates thyroid hyperplasia, which is reversible on withdrawal of KA.