Effect of 3-methylcholanthrene on rat uterus: Uterine growth and mechanism of action of 3-methylcholanthrene

Abstract

This study has been undertaken to examine the effect of 3- methylcholanthrene (3MC) on rat uterine growth and to understand the mechanism of action of 3MC in rat uterus. After diethylstilbesterol(DES) or tamoxifen(TAM) or 3MC or DES plus TAM or DES plus 3MC was administered into immature female rats, uterine weight of each group was measured. DES treatment resulted in 4-fold increase in uterine weight over com oil-treated uteri. 3MC treatment had no effect on uterine weight but, DES stimulated uterine weight was inhibited by 3MC concomitant treatment. While TAM alone treatment showed slight increase in uterine weight, inhibited uterine growth stimulated by DES when it was administered with DES concomitantly. Affinity of estradiol for estrogen receptor in the rat uterus was determined via direct binding assay with [ 3H]estradiol and the relative binding affinities of 3MC and TAM were estimated by competition assay. Estradiol turned out to have high affinity for rat uterine estrogen receptor (Kd=0.4 nM). The relative binding affinities of TAM and 3MC were 1% and 4.7% that of DES for rat uterine estrogen receptor, respectively. 3MC was shown to have similar affinity for rat uterine estrogen receptor to that of TAM. Effects of DES, 3MC and TAM administration in vivo on rat uterine estrogen receptor level were examined. It was confirmed that the estrogen, DLS and antiestrogen, TAM decreased estrogen receptor levels from rat uterus and also 3MC decreased rat uterine estrogen receptor level when rats were treated with DES, TAM and 3MC in vivo. Data indicates that 3MC acts as an antiestrogen mediated through estrogen receptor system.