Mechanisms of the stimulation of rat uterine peroxidase activity by methoxychlor

Methoxychlor (MXC) has adverse effects on fertility and rat uteri via its active metabolite HPTE (2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane). Uterine peroxidase, a marker of estrogen action, was used to probe potential mechanisms of MXC's adverse effects. Specifically, our objective was to compare the regulation of the effects of estrogen and MXC on uterine peroxidase. Immature female rats were treated with MXC (250 mg/kg; gavage) 24 h prior to the measurement of uterine peroxidase activity, with or without concurrent treatment with actinomycin D, cycloheximide, progesterone, or tamoxifen. MXC alone produced an increase in peroxidase activity. The prior and/or concurrent treatment with the compounds listed blocked the MXC-induced stimulation of peroxidase. These data show similarities between the mechanisms of estrogen MXC action. Both estrogen and MXC act to stimulate uterine peroxidase activity via increased RNA and protein synthesis and this stimulation can be blocked by progesterone and tamoxifen.