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
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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.