WEANLING FEMALE SPRAGUE-DAWLEY RATS ARE NOT SENSITIVE TO THE ANTIESTROGENIC EFFECTS OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD)

Investigators have shown that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCD D) can inhibit certain estrogenic events in vivo and in vitro. To furt her investigate this phenomenon, the effects of estradiol (E(2)) alone or TCDD plus estradiol on several estrogen-dependent parameters were evaluated in weanling female Sprague-Dawley rats. E(2)(10 mu g/kg/day, Postnatal Days (PND) 21 and 22) caused significant increases in relat ive uterine weight and keratinization of the vaginal epithelium (PND 2 3). E(2) significantly reduced uterine estrogen receptor (ER) protein levels and serum FSH levels, with a trend toward reduction of ER mRNA levels. None of these parameters were affected by pretreatment with 20 , 40, or 80 mu g/kg TCDD (PND 19). Uterine progesterone receptor level s were not affected by E(2) or TCDD in the present study. In contrast, TCDD significantly decreased body weight (40 or 80 mu g/kg) by PND 21 , significantly decreased relative thymic weights, and significantly i ncreased relative hepatic weights (20, 40, and 80 mu g/kg, by PND 23). In addition, TCDD dramatically induced CYPIA1 hepatic mRNA levels, in dicating that TCDD was properly delivered and could mediate other well -documented Ah receptor-dependent events. Thus, weanling female Spragu e-Dawley rats are not sensitive to the antiestrogenic effects of TCDD at doses which cause overt toxicity. The results provide evidence that the previously reported antiestrogenic effects of TCDD are probably s pecies, strain, and age dependent. (C) 1995 Academic Press, Inc.