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The effect of triclosan on the uterotrophic response to extended doses of ethinyl estradiol in the weanling rat
Citation:
Louis, G., D. Hallinger, AND T. Stoker. The effect of triclosan on the uterotrophic response to extended doses of ethinyl estradiol in the weanling rat. REPRODUCTIVE TOXICOLOGY. Elsevier Science Ltd, New York, NY, 36:71-77, (2013).
Impact/Purpose:
Triclosan potentiates the estrogenic response of ethinyl estradiol in the uterus of the rat. This study is a continuation of a previous report and extends the dose response of ethinyl estradiol examined.
Description:
Triclosan (TCS), a broad-spectrum antimicrobial agent found in many personal care products, has been detected in humans and has been shown to interact with endocrine systems in rats. We previously reported that TCS potentiated the estrogenic effect of ethinyl estradiol (EE) on uterine growth in female rats exposed to a combination of EE (3µg/kg) and TCS (4.69-37.5mg/kg). Here we further characterized the ability of TCS to augment the EE-induced response by evaluating the effect of combined exposures to an extended range of EE doses (0.125-3μg/kg) and TCS doses (2.3-18.75mg/kg). Exposure to EE alone at doses as low as 0.25μg/kg significantly increased uterine weight compared to vehicle, but 0.125μg/kg EE had no effect. The lowest doses of EE+TCS that induced a significant increase in uterine weight above EE alone was 0.5μg/kg EE+9.375mg/kg TCS. Combined exposures to 0.125 or 0.25μg/kg EE with any dose of TCS tested failed to illicit a uterine growth response. Thus, TCS enhanced the uterine response to EE at doses of EE below those in our previous study. These observations were confirmed by increases in uterine epithelial cell height. EE alone downregulated uterine estrogen receptor expression that was further decreased after cotreatment with TCS. In contrast, expression of estrogen-dependent genes, calbindin-D9k and IGF-1 was upregulated by EE alone, but was differentially regulated by cotreatment with TCS. The potentiation of EE by TCS was observed at EE doses comparable to those used in oral contraceptives and post-menopausal management for women.