Comparative effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and progesterone on estrogenic responses in rats

The relative activities of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and progesterone were determined in the 25 day old female Long Evans rats. Both 2,3,7,8-TCDD and progesterone treatment result in significant decreases in nuclear and cytosolic progesterone and estrogen receptor (PR and ER). The major difference between the two compounds is associated with the relative persistence of the effects of 2,3,7,8-TCDD. Using an in vitro uterine strip assay, similar effects on ER and PR levels were observed following 2,3,7,8-TCDD treatment on the uteri. Protein and RNA synthesis inhibitors, namely puromycin, cycloheximide and actinomycin D were preincubated with the uteri prior to progesterone or 2,3,7,8-TCDD treatment. Previous studies by Leavitt and coworkers suggested that progesterone-induced decreases in nuclear ER levels were dependent on both RNA and protein synthesis. With 2,3,7,8-TCDD, the protein synthesis inhibitors did not prevent the observed decreases in ER and PR levels, whereas the RNA synthesis inhibitor actinomycin D inhibited the effects of 2,3,7,8-TCDD on uterine ER and PR levels. These results suggest that the mechanism of 2,3,7,8-TCDD-mediated decreases in ER and PR levels is different from that of progesterone.