The effect of raloxifene on the uterine weight response in immature mice exposed to 17 beta-estradiol, 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane and methoxychlor

OBJECTIVE: The purpose of this study was to determine the effects of raloxi fene on the uterine responses to both estradiol and the environmental estro gens 1,1,1 -trichloro-2,2-bis(p-chlorophenyl)ethane and methoxychlor in imm ature mice. STUDY DESIGN: Immature female mice received the following compounds alone o r in combination: sesame oil (control), 17 beta-estradiol 1 mg/kg body weig ht, tamoxifen 1 mg/kg body weight, raloxifene 5 mg/kg body weight, 1,1,1 -t richloro-2,2-bis(p-chlorophenyl)ethane 10 mg/kg body weight, and methoxychl or 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 m L sesame oil. Approximately 24 hours after the final treatment the animals were killed and the uteri were excised, stripped of remaining fat and mesen tery, and weighed. Groups were analyzed with analysis of variance. RESULTS: Estradiol increased the mean (+/-SE) weight from 20 +/- 6.4 mg (wa s measured in the control group) to 77 +/- 6.2 mg. Tamoxifen increased uter ine weight to 60 +/- 6.2 mg; however, raloxifene had no effect on uterine w eight. 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 17 beta-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 metho xychlor, it completely blocked the uterine weight gain induced by either xe noestrogen. CONCLUSION: Raloxifene blocked the xenoestrogens 1,1,1 -trichloro-2,2-bis(p -chlorophenyl)ethane and methoxychlor but did not block 17 beta-estradiol i n the mouse model described. These results suggest that the xenoestrogens e xert their estrogenic activities through a different site on the estrogen r eceptor or through a different mechanism than 17 beta-estradiol.