Uterotrophic Assay Using Ovariectomized Female Rats with Sub-cutaneous Administration

Kim, Hyung-Sik; Han, Soon-Young; Lee, Rhee-Da; Kil, Kwang-Sup; Park, Kui-Lea

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자료유형: 학술저널

저자정보: Kim, Hyung-Sik (Reproductive and Developmental Toxicology Division, National Institute of Toxicological Research) Han, Soon-Young (Reproductive and Developmental Toxicology Division, National Institute of Toxicological Research) Lee, Rhee-Da (Reproductive and Developmental Toxicology Division, National Institute of Toxicological Research) Kil, Kwang-Sup (Reproductive and Developmental Toxicology Division, National Institute of Toxicological Research) Park, Kui-Lea (Reproductive and Developmental Toxicology Division, National Institute of Toxicological Research)

저널정보: 한국응용약물학회 The journal of applied pharmacology : the official journal of the Korean Society of Applied Pharmacology The journal of applied pharmacology : the official journal of the Korean Society of Applied Pharmacology 제8권 제1호

발행연도: 2000.1

수록면: 78 - 83 (6page)

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The objective of this study was to prevalidate the Organization for Economic Cooperation and Development's (OECD) rodent uterotrophic assay as a test method for screening of potential endocrine disrupting chemicals (EDCs). This study was conducted exactly as described in the OECD protocol documents. A positive control substance, 17$\alpha$-ethinyl estradiol (EE), was administered daily for three days to ovariectomized (OVX) Sprague-Dawley rats at various doses for determine the dose-response curve. Additionally, a pure antiestrogenic chemical, ZM189, 154 was administered to OVX rats at the same time EE to determine the effectiveness of the material against blocking the estrogenic effects of EE. At higher concentration of EE (10 $\mu\textrm{g}$/kg), a statistically significant difference in body weight gain and food consumption was observed compared to vehicle controls. In uterine responses, EE produced a dose-related increase in uterus weights compared to vehicle control. These increases were statistically significant at the >1.0 $\mu\textrm{g}$/kg doses. However, a similar dose-response relationship was not observed in vagina weight. A comparison of the two groups receiving ZM189,154 (0.1 and 1.0 mg/kg) with 0.3 $\mu\textrm{g}$/kg of EE and the group receiving only 0.3 $\mu\textrm{g}$/kg of EE showed dose-related decreases in uterus weights. However, statistical significance was shown in 1.0 mg/kg of ZM189,154. In conclusion, administration of EE produced a dose-related increase in uterine (wet and blotted) weights. Additionally, the 1.0mg/kg dose of ZM189,154 was effective in blocking the estrogenic activity of EE. These data suggest 3-day uterotrophic assay using OVX rats may serve as a good tool for EDCs screening.

#uterotrophic assay #ovariectomized #17-ethinyl estradiol #ZM 189,154

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