2,3,7,8-Tetrachlorodibenzo-p-dioxin inhibition of 17β-estradiol-induced increases in rat uterine epidermal growth factor receptor binding activity and gene expression

Treatment of immature female Sprague-Dawley rats with 17β-estradiol (5 μg/animal) resulted in an increase in uterine epidermal growth factor (EGF) receptor binding activity. Moreover, in a separate study it was also shown that 17β-estradiol increased steady-state levels of rat uterine EGF receptor mRNA as determined by Northern analysis. In contrast, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) caused a dose-response decrease in constitutive rat uterine EGF receptor binding activity and this was paralleled by a decrease in steady-state levels of uterine EGF receptor mRNA. Cotreatment of the animals with both TCDD (16 nmol/kg) and 17β-estradiol (5 μg/rat) gave results which showed that TCDD significantly inhibited the estrogen-induced increases in rat uterine EGF receptor binding activity and EGF receptor mRNA levels. These results further extend the range of antiestrogenic properties of TCDD and suggest that the inhibition of growth factor expression may play a role in the growth-inhibiting properties of TCDD in estrogen-responsive tissues or cells.