Abstract
Originally identified for its capacity to inhibit the random migration of macrophages in vitro, macrophage migration inhibitory factor (MIF) is now recognized as a multifunctional cytokine that modulates the immune response and acts as a growth and angiogenic factor. Recent studies showed that MIF is expressed in the human endometrium across the menstrual cycle as well as in chorionic villi from first-trimester human placenta, which suggests an involvement of MIF in reproduction. Herein, we report that human chorionic gonadotropin (hCG), a glycoprotein hormone that plays a critical role in the initiation and maintenance of pregnancy, markedly stimulates MIF expression in endometrial stromal cells. Cell treatment with hCG resulted in a dose-dependent increase in MIF protein secretion and mRNA steady-state levels, as shown by immunocytochemistry, ELISA, and RT-PCR. Assessment of MIF mRNA half-life showed that hCG treatment had no significant effect on MIF mRNA stability (P = 0.08). However, nuclear transcription assays (run-on) revealed that hCG acts predominantly by up-regulating MIF gene transcription. These data clearly indicate that MIF can mediate hCG effects on the human endometrium and, in view of the immunomodulatory and angiogenic properties of MIF, reveal a new mechanism by which hCG sustains human pregnancy and promotes embryonic growth.
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