Carcinogenesis, Vol. 20, No. 8, 1567-1572,
August 1999
© 1999 Oxford University Press
Carcinogenesis |
Changes in thyroid function during development of thyroid hyperplasia induced by kojic acid in F344 rats
Department of Cancer Research, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553 and
1 Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan
To clarify the mechanism of tumorigenesis by kojic acid (KA), dose and time dependence of iodine uptake in the thyroid gland and serum thyroid stimulating hormone (TSH) and thyroid hormone levels were investigated in F344 rats fed a diet containing 2% KA. After 4 weeks, thyroid hyperplasia was apparent in males, associated with a decrease in 125I uptake into the thyroid gland to only 3% of that in controls. The serum triiodothyronine (T3) and thyroxine (T4) levels dropped to 0.36 ng/ml, 1.7 µg/dl from the initial values of 0.61 ng/ml, 4.0 µg/dl and TSH increased seven times to 15 ng/ml. In females, the effects on thyroid weight and 125I uptake were less prominent, although the changes in serum T3, T4 and TSH levels were similar to those in males. Time-dependent changes in serum T3, T4 and TSH levels correlated with the inhibition of iodine uptake in the thyroid. Inhibition of organic iodine formation was only observed after 3 weeks treatment. On return to the control diet, normal serum T3, T4 and TSH levels became evident within 48 h in both sexes. These data suggest that KA interrupts thyroid function, primarily by inhibiting iodine intake, consequently causing a decrease in serum T3 and T4. Increased TSH from the pituitary gland in turn stimulates thyroid hyperplasia, which is reversible on withdrawal of KA.
Abbreviations: HE, hematoxylin and eosin; KA, kojic acid; T3, triiodothyronine; T4, thyroxine; TSH, thyroid stimulating hormone; UDP-GT, uridine diphosphate glucuronosyltransferase
2 To whom correspondence should be addressed Email: nfjm{at}ipc.hiroshima-u.ac.jp
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