title: Progestin-induced heart and neural crest derivatives expressed transcript 2 is associated with fibulin-1 expression in human endometrial stromal cells.
abstract: OBJECTIVE
  To investigate whether heart and neural crest derivatives expressed transcript 2 (HAND2) regulates fibulin-1 (FBLN1) expression during decidualization of human endometrial stromal cells (ESCs).
  
  
  METHODS
  In vitro experiment.
  
  
  METHODS
  Research laboratory.
  
  
  METHODS
  Twenty-four patients undergoing hysterectomy for benign reasons.
  
  
  METHODS
  ESCs were cultured with various progestins (medroxyprogesterone acetate [MPA], norethisterone, levonorgestrel, dienogest, and P), E(2), dexamethasone, and/or 8-bromoadenosine 3', 5'-cyclic monophosphate (8-Br-cAMP). HAND2 and FBLN1 were silenced by small interfering RNA technology.
  
  
  METHODS
  HAND2 and FBLN1 expression levels were assessed by real-time polymerase chain reaction and Western blot analysis.
  
  
  RESULTS
  MPA or E(2) + MPA increased HAND2 mRNA levels in ESCs in a time- and dose-dependent manner, and this stimulatory effect was blocked by RU-486 (P receptor antagonist). HAND2 was increased by E(2) + MPA earlier than FBLN1. Simultaneous MPA and 8-Br-cAMP treatment synergistically enhanced HAND2 mRNA levels. P and all the progestins significantly increased HAND2 mRNA levels, whereas E(2), 8-Br-cAMP, or dexamethasone alone had no effect. Silencing of HAND2 expression significantly reduced FBLN1 expression, whereas FBLN1 silencing had no effect on HAND2 expression.
  
  
  CONCLUSIONS
  These results suggest that progestin-induced HAND2 contributes to FBLN1 expression in human ESCs.
authors.affiliation: Department of Obstetrics and Gynecology, Kansai Medical University, Osaka, Japan.
authors.forename: Hisayuu
authors.initials: H
authors.lastname: Cho
authors.affiliation: Department of Obstetrics and Gynecology, Kansai Medical University, Osaka, Japan. Electronic address: hokada@hirakata.kmu.ac.jp.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Okada
authors.affiliation: Department of Obstetrics and Gynecology, Kansai Medical University, Osaka, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tsuzuki
authors.affiliation: Department of Obstetrics and Gynecology, Kansai Medical University, Osaka, Japan.
authors.forename: Akemi
authors.initials: A
authors.lastname: Nishigaki
authors.affiliation: Department of Obstetrics and Gynecology, Kansai Medical University, Osaka, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Yasuda
authors.affiliation: Department of Obstetrics and Gynecology, Kansai Medical University, Osaka, Japan.
authors.forename: Hideharu
authors.initials: H
authors.lastname: Kanzaki
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D003656:Decidua / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004717:Endometrium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D012739:Gonadal Steroid Hormones / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D011372:Progestins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D015124:8-Bromo Cyclic Adenosine Monophosphate; D051792:Basic Helix-Loop-Helix Proteins; D002135:Calcium-Binding Proteins; D004967:Estrogens; D012739:Gonadal Steroid Hormones; D011372:Progestins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C498765:HAND2 protein, human; C060820:fibulin