ALTERATIONS IN THYROID-FUNCTION IN FEMALE SPRAGUE-DAWLEY RATS FOLLOWING CHRONIC TREATMENT WITH 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN

Citation
Ch. Sewall et al., ALTERATIONS IN THYROID-FUNCTION IN FEMALE SPRAGUE-DAWLEY RATS FOLLOWING CHRONIC TREATMENT WITH 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN, Toxicology and applied pharmacology, 132(2), 1995, pp. 237-244
Citations number
48
Categorie Soggetti
Pharmacology & Pharmacy",Toxicology
ISSN journal
0041008X
Volume
132
Issue
2
Year of publication
1995
Pages
237 - 244
Database
ISI
SICI code
0041-008X(1995)132:2<237:AITIFS>2.0.ZU;2-W
Abstract
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a multisite carcinogen. Although the hepatocarcinogenic actions of TCDD have received the most attention, it has been demonstrated in several rodent carcinogenicity bioassays that TCDD causes a dose-related increase in thyroid follicu lar cell adenomas and carcinomas. The purpose of the present experimen t was to investigate the dose-response relationship for thyroid functi on alterations in female Sprague-Dawley rats following chronic treatme nt with TCDD. TCDD was administered via oral gavage biweekly for 30 we eks at average daily equivalent doses of 0.1-125 ng/kg/day, thereby mo re than encompassing the dose range historically used in previous TCDD rodent bioassays. The endpoints examined include serum levels of thyr oxine (T4), triiodothyronine (T3), and thyroid-stimulating hormone (TS H). In addition, the induction of the dioxin-responsive genes UDP-gluc uronosyltransferase-1 (UGT1) and cytochrome P450 1A1 (CYP1A1) in liver were measured using reverse-transcriptase-polymerase chain reaction ( RT-PCR). In agreement with previous hypotheses, TCDD appears to alter thyroid function via a secondary mechanism, namely increased excretion of T4-glucuronide resulting from TCDD induction of UGT1. The observed follicular cell hyperplasia and hypertrophy are consistent with the o bserved elevated TSH levels and may represent the early stages in the progression of thyroid carcinogenesis. Therefore, TCDD induces alterat ions in thyroid hormone function, probably as a result of chronic pert urbations of liver-pituitary-thyroid axis. (C) 1995 Academic Press, In c.