title: Inhibition of thyroid iodine uptake and organification in rats treated with kojic acid.
abstract: In order to elucidate the mechanisms of reduction of serum thyroid hormones caused by continuous administration of kojic acid (KA) and its thyroid tumor-promotion effects, male F344 rats were given pulverized basal diet containing 0.008%, 0.03%, 0.125%, 0.5%, or 2% KA for 4 weeks. As an untreated control group, additional rats were given basal diet alone for the same period. The thyroid 125I uptake was significantly decreased in the groups receiving 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 along with pronounced elevation of serum (TSH). Both absolute and relative thyroid weights were significantly increased in the groups receiving 0.5% of KA or more. Histopathologically, decreased colloid in the thyroid follicles and follicular cell hypertrophy in the thyroid were apparent at high incidences in the groups given 0.03% or more. In addition, thyroid capsular fibrosis was evident in all rats of the 2% KA group. In quantitative morphometrical analysis, the ratio of the area of follicular epithelial cells to the area of colloids was significantly increased in the groups given 0.03% KA or more. The results suggest that KA alteration of thyroid-related hormone levels in the 2% KA group are due to inhibition of iodide uptake and iodine organification in the thyroid, with tumor-promoting effects on development of thyroid proliferative lesions, probably secondary to prolonged serum TSH stimulation resulting from negative feedback through the pituitary-thyroid axis.
authors.affiliation: Division of Pathology, National Institute of Health Sciences, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tamura
authors.forename: K
authors.initials: K
authors.lastname: Mitsumori
authors.forename: H
authors.initials: H
authors.lastname: Onodera
authors.forename: N
authors.initials: N
authors.lastname: Fujimoto
authors.forename: K
authors.initials: K
authors.lastname: Yasuhara
authors.forename: K
authors.initials: K
authors.lastname: Takegawa
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D004032:Diet; D007454:Iodides / Q000378:metabolism*; D008099:Liver / Q000187:drug effects; D008297:Male; D009183:Mycotoxins / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D010902:Pituitary Gland / Q000187:drug effects; D011753:Pyrones / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism
chemical_list: D002273:Carcinogens; D007454:Iodides; D009183:Mycotoxins; D011753:Pyrones; C011890:kojic acid