title: Disparate effects of relaxin and TGFbeta1: relaxin increases, but TGFbeta1 inhibits, the relaxin receptor and the production of IGFBP-1 in human endometrial stromal/decidual cells.
abstract: BACKGROUND
  The purpose of this study was to determine the effect of progestin, relaxin (RLX) and transforming growth factor beta1 (TGFbeta1) on the content of relaxin receptor (LGR7) mRNA. The effect of RLX on insulin-like growth factor binding protein-1 (IGFBP-1) production was determined to evaluate the biological function of RLX/receptor in human endometrial cells.
  
  
  RESULTS
  The levels of LGR7 mRNA and the effect of hormones were determined by real-time PCR in endometrial cells. LGR7 mRNA was found to be relatively abundant in endometrial glands and decidual cells and much less in endometrial stromal cells. In stromal cells, medroxyprogesterone acetate (MPA), or MPA plus RLX, significantly increased the LGR7 mRNA and RLX alone had little effect. In decidual cells, RLX increased LGR7 mRNA in a dose- and time-dependent fashion. TGFbeta1 reduced the LGR7 mRNA. In stromal cells, MPA alone caused a slight increase (2-4-fold) of the production rate of IGFBP-1 whereas MPA plus RLX synergistically increased (>40-fold) the IGFBP-1 production. In decidual cells in which the basal production rate was already approximately 50-fold higher than in stromal cells, RLX alone caused an additional increase (>30-fold) on the production rate. TGFbeta1 inhibited the IGFBP-1 production.
  
  
  CONCLUSIONS
  The present study showed that in undifferentiated endometrial stromal cells, progestin increases the RLX receptor content to enhance the effect of RLX on the target gene (IGFBP-1). In decidual cells, RLX alone up-regulates its receptor, resulting in a large scale induction of IGFBP-1. TGFbeta1 has an inhibitory effect on LGR7 and IGFBP-1.
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, State University of New York at Stony Brook, NY 11794-8091, USA.
authors.forename: J
authors.initials: J
authors.lastname: Mazella
authors.forename: M
authors.initials: M
authors.lastname: Tang
authors.forename: L
authors.initials: L
authors.lastname: Tseng
mesh_terms: D002478:Cells, Cultured; D003656:Decidua / Q000166:cytology / Q000378:metabolism; D004357:Drug Synergism; D004717:Endometrium / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D017258:Medroxyprogesterone Acetate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics; D011372:Progestins / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D018000:Receptors, Peptide / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D012065:Relaxin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D017154:Stromal Cells / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
chemical_list: D018970:Insulin-Like Growth Factor Binding Protein 1; D008565:Membrane Proteins; D011372:Progestins; D012333:RNA, Messenger; C417543:RXFP1 protein, human; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C033395:relaxin receptors; D012065:Relaxin; D017258:Medroxyprogesterone Acetate