title: Dickkopf-1, an inhibitor of Wnt signaling, is regulated by progesterone in human endometrial stromal cells.
abstract: BACKGROUND
  Some members of the Wnt family, including ligands, receptors, inhibitors, and signaling components, are expressed in human endometrium. Dickkopf-1 (Dkk-1), a potent inhibitor of the Wnt signaling pathway, was recently found to be up-regulated in decidualizing endometrial stromal cells during the secretory phase of the menstrual cycle, suggesting regulation by progesterone.
  
  
  OBJECTIVE
  To test the hypothesis that progesterone regulates Dkk-1 expression in human endometrial stromal cells, we investigated the following effects on stromal cell expression of Dkk-1 mRNA and protein: decidualizing stimuli (progesterone or cAMP), RU486 (an inhibitor of progesterone action), and withdrawal of progesterone.
  
  
  RESULTS
  Short-term treatment (up to 72 h, which corresponds to the full decidualized phenotype in response to cAMP and an early response to progesterone) did not reveal regulation of Dkk-1 mRNA or protein by cAMP but did show induction of Dkk-1 expression when the cells were treated with progesterone, an effect that was blocked by RU486. In long-term cultures (from 14 to 23 d, which corresponds to the full decidualized phenotype in response to progesterone), a significant increase in Dkk-1 mRNA and protein production was observed. Addition of RU486 or withdrawal of progesterone after long-term decidualization resulted in a decrease of Dkk-1 mRNA and protein to control levels. Estradiol alone had no effect on stromal Dkk-1 expression.
  
  
  CONCLUSIONS
  These data strongly support regulation by progesterone of Dkk-1 mRNA synthesis and protein expression in human endometrial stromal cells and that the response is specific for progesterone and independent of cAMP and estradiol.
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California-San Francisco, 505 Parnassus Avenue M1496, San Francisco, CA 94143-0132, USA.
authors.forename: Suzana
authors.initials: S
authors.lastname: Tulac
authors.forename: Michael T
authors.initials: MT
authors.lastname: Overgaard
authors.forename: Amy E
authors.initials: AE
authors.lastname: Hamilton
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Jumbe
authors.forename: Ernest
authors.initials: E
authors.lastname: Suchanek
authors.forename: Linda C
authors.initials: LC
authors.lastname: Giudice
mesh_terms: D000328:Adult; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology; D004717:Endometrium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015735:Mifepristone / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism; D051153:Wnt Proteins / Q000502:physiology*
chemical_list: C501126:DKK1 protein, human; D006727:Hormone Antagonists; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D051153:Wnt Proteins; D015735:Mifepristone; D011374:Progesterone; D000242:Cyclic AMP