the expression and function of NK receptors [47]. Previous study showed that the suppression of human lymphocyte proliferation by cortisol can be reversed by mifepristone; however, the suppression by progesterone is not affected [8]. In the present study, we found that activation of the ERK pathway by mifepristone was blocked by the presence of cortisol. This suggests that mifepristone can promote activation of the ERK pathway through the GR. Moreover, we found that when ERK activation was inhibited by PD98059 or U0126, neither uNK cell- mediated cytotoxicity nor perforin expression was influenced by either cortisol or mifepristone. This implied that the activation of ERK by mifepristone was involved in the regulation of uNK cell- mediated cytotoxicity. Usually, the MAPK signaling pathway is activated through membrane receptors. Although GR is a member of the nuclear hormone receptor superfamily, it has been shown that glucocorticoids induce the expression of the glucocorticoid- leucine zipper (GILZ) and MAPK phosphatase-1 (MKP-1). The induction of GILZ and MKP-1 genes provides a mechanism by which GR can modulate the MAPK pathway [48]. NK cell function is controlled by signals generated from inhibitory and stimulatory receptors. Ligation of the stimulatory receptor leads to activation of a cascade of intracellular signaling events, resulting in exocytosis of granules to lyse target cells [49,50]. Many receptor signaling molecules, including NKG2D (the best-characterized activating receptor of NK cells), are located References 1. Spitz IM (2006) Progesterone receptor antagonists. Curr Opin Investig Drugs 7: 882–890. 2. Li A, Felix JC, Minoo P, Amezcua CA, Jain JK (2005) Effect of mifepristone on proliferation and apoptosis of Ishikawa endometrial adenocarcinoma cells. Fertil Steril 84: 202–211. 3. 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