title: Marked increase in macrophage migration inhibitory factor synthesis and secretion in human endometrial cells in response to human chorionic gonadotropin hormone.
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.
authors.affiliation: Unité d'Endocrinologie de la Reproduction, Laboratoire d'Endocrinologie de la Reproduction, Centre de Recherche, Hôpital Saint-François d'Assise, 10 rue de l'Espinay, Local D0-711, Québec, Québec, Canada G1L 3L5. ali.akoum@crsfa.ulaval.ca
authors.forename: Ali
authors.initials: A
authors.lastname: Akoum
authors.forename: Christine N
authors.initials: CN
authors.lastname: Metz
authors.forename: Mathieu
authors.initials: M
authors.lastname: Morin
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D004717:Endometrium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D006063:Chorionic Gonadotropin; D008263:Macrophage Migration-Inhibitory Factors; D012333:RNA, Messenger