title: Progesterone Inhibits Leptin-Induced Invasiveness of BeWo Cells.
abstract: BACKGROUND
  This study investigated the roles of progesterone and leptin in placenta invasion, which is closely related to pregnancy prognosis. We examined the effects of leptin and progesterone on the invasion of BeWo cells, a human trophoblastic cell line, and the effect of concurrent treatment.
  
  
  METHODS
  Cells were treated with leptin (0, 5, 50, or 500 ng/mL) or progesterone (0, 2, 20, or 200 µM) and cultured in an invasion assay. Cells treated with 500 ng/mL leptin were also treated with progesterone (0, 2, 20, or 200 µM) in the invasion assay for 48 h. The number of cells that invaded the lower surface was counted in five randomly chosen fields using a light microscope with a 200× objective. The mRNA expression levels of MMP-9, TIMP1, TIMP2, and E-cadherin were detected by semi-quantitative PCR.
  
  
  RESULTS
  Invasion of BeWo cells was promoted by leptin and influenced by both leptin concentration and treatment duration. Invasion was most effective at 500 ng/mL leptin and 48 h culture. Leptin-induced invasiveness was suppressed by progesterone in a dose-dependent manner. Leptin significantly decreased the expression levels of TIMP1 and E-cadherin, whereas progesterone significantly decreased expression of MMP-9 and significantly increased levels of TIMP1, TIMP2, and E-cadherin.
  
  
  CONCLUSIONS
  Leptin promotes invasion of BeWo cells, and progesterone suppresses leptin-induced invasion by regulating the expressions of MMP-9, TIMP1, TIMP2, and E-cadherin. The balance between leptin and progesterone may play an important role in human placenta formation during early pregnancy.
authors.affiliation: 1. Department of Obstetrics and Gynecology, College of Medicine, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Republic of Korea.
authors.forename: Yun Sung
authors.initials: YS
authors.lastname: Jo
authors.affiliation: 1. Department of Obstetrics and Gynecology, College of Medicine, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Republic of Korea.
authors.forename: Gui Se Ra
authors.initials: GS
authors.lastname: Lee
authors.affiliation: 1. Department of Obstetrics and Gynecology, College of Medicine, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Republic of Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Nam
authors.affiliation: 2. Department of Obstetrics and Gynecology, College of Medicine, Bucheon St. Mary's Hospital, The Catholic University of Korea, Bucheon, Republic of Korea.
authors.forename: Sa Jin
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D015820:Cadherins / Q000235:genetics; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D020738:Leptin / Q000494:pharmacology*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D009361:Neoplasm Invasiveness; D011374:Progesterone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics; D014327:Trophoblasts / Q000737:chemistry / Q000187:drug effects*
chemical_list: D015820:Cadherins; D020738:Leptin; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D011374:Progesterone; D020780:Matrix Metalloproteinase 9
keywords: Cadherins; Leptin; Matrix Metalloproteinase; Placenta; Progesterone; Tissue Inhibitor of Metalloproteinases; Trophoblast