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The production of leukemia inhibitory factor (LIF) is suggested to be critical for the successful implantation of blastocysts into decidua, because LIF expression is essential for the implantation of mouse blastocytes. We investigated the regulation of LIF production by decidual cytokines and steroid hormones. Stimulation of decidual cells by interleukin-1, tumor necrosis factor alpha, or transforming growth factor beta augmented LIF production in a dose-dependent manner. Moreover, estradiol, a steroid hormone that increases during ovulation and early pregnancy, also enhanced LIF production in a dose-dependent manner. These responses were blocked by protein kinase C (PKC) inhibitor but not by other kinase inhibitors, suggesting an important role of PKC in decidual LIF production mediated by cytokines and estradiol. We also showed that stimulating decidual cells with LIF failed to stimulate DNA synthesis and prolactin production in these cells. In summary, LIF was mainly localized in the decidual glands and stroma, and its production was increased by cytokines and estradiol in a dose-dependent fashion; but stimulation of decidual cells by LIF did not influence their proliferation or their prolactin production.

Human Decidual Cell Biosynthesis of Leukemia Inhibitory Factor: Regulation by Decidual Cytokines and Steroid Hormones1