MECHANISMS OF THE STIMULATION OF RAT UTERINE PEROXIDASE-ACTIVITY BY METHOXYCHLOR

Methoxychlor (MXC) has adverse effects on fertility and rat uteria via its active metabolite HPTE (2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroe thane). Uterine peroxidase, a marker of estrogen action, was used to p robe 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 peroxida se activity, with or without concurrent treatment with actinomycin D, cycloheximide, progesterone, or tamoxifen. MXC alone produced an incre ase in peroxidase activity. The prior and/or concurrent treatment with the compounds listed blocked the MXC-induced stimulation of peroxidas e. These data show similarities between the mechanisms of estrogen MXC action. Both estrogen and MXC act to stimulate uterine peroxidase act ivity via increased RNA and protein synthesis and this stimulation can be blocked by progesterone and tamoxifen.