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In the present study, we found that the Grin2d gene of mouse possessed half\u2010sites of the estrogen\u2010responsive element (ERE) in the 3\u2032\u2010untranslated region (UTR). Quantitative PCR analysis showed that the reduced Grin2d mRNA expression in the hypothalamus of the ovariectomized mice was restored by estrogen administration. Downregulation of Grin2d mRNA expression was also detected in the hypothalamus of estrogen receptor alpha\u2010knockout female mice. Moreover, estrogen\u2010induced lordosis response was decreased in Grin2d\u2010knockout mice. 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