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MECHANISMS OF THE STIMULATION OF RAT UTERINE PEROXIDASE ACTIVITY BY METHOXYCHLOR
Citation:
Cummings, A. AND J. Metcalf. MECHANISMS OF THE STIMULATION OF RAT UTERINE PEROXIDASE ACTIVITY BY METHOXYCHLOR. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-95/214.
Description:
Methoxychlor (MXC), a pro-estrogenic pesticide, has adverse effects on fertility and affects the rat uterus directly via its active metabolite HPTE. terine peroxidase, a marker of estrogen action, was used to probe the mechanisms through which MXC exerts its activity on the uterus. ur objective was to compare the regulation,by various inhibitors, of estrogen and MXC effects on uterine peroxidase. mmature female rats were treated with MXC (250 mg/kg;gavage) 24 hrs prior to the measurement of uterine peroxidase activity, with or without concurrent treatment with actinomycin D, cycloheximide, progesterone, tamoxifen, or 17B-estradiol MXC alone produced a dose dependent increase in uterine peroxidase activity, as does estrogen. The pre-and/or concurrent (with MXC) treatment with each of the compounds listed blocked the MXC-induced stimulation of uterine peroxidase activity. hen 17B-estradiol and MXC were combined, following pretreatment with MXC, MXC blocked the estrogen-induced stimulation of uterine peroxidase activity. hese data show a similarity between the mechanism of estrogen action and the mechanisms of 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. inally, we present data to suggest that MXC also can act as an anti-estrogen at certain doses.