Mechanism responsible for hyperplasia of rat thyroid induced by gestational and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

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Effects of gestational and lactational exposure to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) on pup thyroids were investigated in the rat. Pregnant Holtzman rats, TCDD-sensitive strain, were given a single oral dose of 200ng or 800ng TCDD/kg on gestational day (GD) 15. Parameters related to the thyroid functions were examined on postnatal days (PNDs) 21 and 49. Thyroxin (T4) levels in pup serum were decreased significantly on PND21 in the TCDD-exposed groups, but a significant increase in T4 levels were found on PND49 in the higher dose group. The serum levels of thyroid stimulating hormone (TSH) was more than 2-fold higher in male offspring as compared to the control on PNDs 21 and 49 at the higher dose of TCDD (800ng/kg). A significant induction of UDP-glucuronosyltransferase-1 (UGT1) gene by TCDD was observed on PND 21, but returned to basal levels on PND 49. Gene expression of cytochrome P4501A1 (CYP1A1) was markedly induced in the liver treated with TCDD. A single oral exposure to TCDD (800ng/kg) during perinatal period resulted in hyperplasia of the thyroid gland of pups on PND 49. This was confirmed by proliferating cell nuclear antigen (PCNA) immunocytochemistry. We thus conclude that gestational and lactational exposure to TCDD disrupts thyroid hormone homeostasis, which results in a sustained excessive secretion of TSH, leading to the hyperplasia of thyroid follicular cells.
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