ABSTRACT
OBJECTIVE: The purpose of this study was to determine the effects of raloxifene on the uterine responses to both estradiol and the environmental estrogens 1,1,1-trichloro-2, 2-bis(p-chlorophenyl)ethane and methoxychlor in immature mice. STUDY DESIGN: Immature female mice received the following compounds alone or in combination: sesame oil (control), 17beta-estradiol 1 mg/kg body weight, tamoxifen 1 mg/kg body weight, raloxifene 5 mg/kg body weight, 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane 10 mg/kg body weight, and methoxychlor 10 mg/kg body weight. The animals were treated subcutaneously once a day for 5 consecutive days with the compound or compounds of interest in 0.1 mL sesame oil. Approximately 24 hours after the final treatment the animals were killed and the uteri were excised, stripped of remaining fat and mesentery, and weighed. Groups were analyzed with analysis of variance. RESULTS: Estradiol increased the mean (+/-SE) weight from 20 +/- 6.4 mg (as measured in the control group) to 77 +/- 6.2 mg. Tamoxifen increased uterine weight to 60 +/- 6.2 mg; however, raloxifene had no effect on uterine weight. Both 1,1,1-trichloro-2, 2-bis(p-chlorophenyl)ethane and methoxychlor increased uterine weight significantly, to 82 +/- 2.4 mg and 35 +/- 6.0 mg respectively. When raloxifene was coadministered with 17beta-estradiol it did not block the increase in uterine weight; however, when raloxifene was coadministered with 1,1,1-trichloro-2, 2-bis(p-chlorophenyl)ethane or methoxychlor, it completely blocked the uterine weight gain induced by either xenoestrogen. CONCLUSION: Raloxifene blocked the xenoestrogens 1,1,1-trichloro-2, 2-bis(p-chlorophenyl)ethane and methoxychlor but did not block 17beta-estradiol in the mouse model described. These results suggest that the xenoestrogens exert their estrogenic activities through a different site on the estrogen receptor or through a different mechanism than 17beta-estradiol.
