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Immunohistochemical localization of thyroid stimulating hormone induced by a low oral dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin in female Sprague–Dawley rats
- Source :
- Toxicology. 171:73-82
- Publication Year :
- 2002
- Publisher :
- Elsevier BV, 2002.
-
Abstract
- We have investigated how a low dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects thyroid hormone regulation, especially in relation to the localization of thyroid stimulating hormone (TSH) in the pituitary and that of thyroxin (T4) of the thyroid in the rat. Female Sprague-Dawley rats were given a single oral administration of TCDD ranging from 1.0 to 4.0 microg/kg body weight (bw), and then tissue specimens were removed on day 7 post-administration. Thyroid hormone concentrations were measured in serum, and the expression of the TCDD-responsive genes, UDP-glucuronosyltransferase-1 (UGT1) and cytochrome P4501A1 (CYP1A1) were examined in the liver. TCDD administration resulted in an increase in both immunostaining intensity and the number of TSH-positive cells in the anterior pituitary. T4 was found to localize only in the follicular lumen of the thyroid in vehicle-treated control rats, while TCDD administration caused a foamy change in the colloid of some follicles, an indication of accelerating the biosynthesis of T4 in the thyroid. By morphometrical analysis, the ratio of parenchymal/lumenal area of the thyroid was found to increase in response to TCDD. TCDD treatment as low as 2.0 microg TCDD/kg bw induced a significant decrease in both serum total T4 (TT4) and free T4 (FT4) concentrations in the rats, with a significant increase in serum TSH levels in the 4.0 microg TCDD/kg bw rats. Serum total triiodothyronine (TT3) level was unchanged in all groups. The UGT1 gene was significantly induced at a TCDD dose as low as 1.0 microg/kg bw in a dose-dependent manner. TCDD concentrations in the serum, liver and adipose tissues were detected in a dose-related fashion. The present immunohistochemical results clearly support the earlier biochemical findings on the perturbation of the thyroid-pituitary axis by TCDD and suggest that UGT1 is an immediate target of a low TCDD exposure that triggers the perturbation.
- Subjects :
- endocrine system
medicine.medical_specialty
Polychlorinated Dibenzodioxins
Thyroid Gland
Thyrotropin
Adipose tissue
Toxicology
Rats, Sprague-Dawley
Anterior pituitary
Thyroid-stimulating hormone
Oral administration
Internal medicine
Cytochrome P-450 CYP1A1
medicine
Animals
heterocyclic compounds
RNA, Messenger
Glucuronosyltransferase
reproductive and urinary physiology
Triiodothyronine
Chemistry
Thyroid
Immunohistochemistry
Rats
Thyroxine
stomatognathic diseases
medicine.anatomical_structure
Endocrinology
Liver
Pituitary Gland
Toxicity
Female
Hormone
Subjects
Details
- ISSN :
- 0300483X
- Volume :
- 171
- Database :
- OpenAIRE
- Journal :
- Toxicology
- Accession number :
- edsair.doi.dedup.....a97c20e52457d671a0b304d1d0f529a6