title: Activin-A and myostatin response and steroid regulation in human myometrium: disruption of their signalling in uterine fibroid.
abstract: BACKGROUND
  Investigation of activin-A (A) and myostatin (M) in human myometrium (HM) and leiomyoma (HL) will explain their involvement in human myometrial pathophysiology.
  
  
  OBJECTIVE
  We aimed to investigate A and M response and steroid regulation in HM. We also evaluated A and M expression and response in HL.
  
  
  METHODS
  Tissues were analyzed and cultured.
  
  
  METHODS
  Patients included fertile (in proliferative phase) and menopausal women undergoing hysterectomy.
  
  
  METHODS
  HM explant cultures were treated with A and M (for Smad-7 mRNA quantification) or estrogen and progesterone (for A and M mRNA quantification). A and M expression levels were also evaluated in menopausal (physiological absence of steroids) HM specimens. A and M and their receptors were evaluated in HL (n = 8, diameter 5-8 cm) compared with their matched HM. HL explants cultures were treated with A and M (for Smad7 mRNA quantification), and, to explain the absence of response, the levels of follistatin, follistatin-related gene (FLRG), and Cripto were evaluated.
  
  
  RESULTS
  A and M increased Smad7 expression in HM explants. A and M mRNAs were both reduced after estradiol treatment, unchanged after progesterone treatment, but were higher in menopausal than fertile (in proliferative phase) specimens. A, M, and FLRG were expressed at higher levels in HL compared with adjacent HM, whereas the receptors, follistatin, and Smad7 mRNAs resulted unchanged. Cripto mRNA was expressed only in HL.
  
  
  CONCLUSIONS
  A and M act on human HM and are regulated by steroids. In HL there is an increase of A, M, FLRG, and Cripto expression.
authors.affiliation: Department of Molecular Pathology and Innovative Therapies, Faculty of Medicine, Polytechnic University of Marche, via Tronto 10/a, 60020 Ancona, Italy. p.ciarmela@univpm.it
authors.forename: Pasquapina
authors.initials: P
authors.lastname: Ciarmela
authors.forename: Enrrico
authors.initials: E
authors.lastname: Bloise
authors.forename: Peter C
authors.initials: PC
authors.lastname: Gray
authors.forename: Patrizia
authors.initials: P
authors.lastname: Carrarelli
authors.forename: Md Soriful
authors.initials: MS
authors.lastname: Islam
authors.forename: Flavio
authors.initials: F
authors.lastname: De Pascalis
authors.forename: Filiberto Maria
authors.initials: FM
authors.lastname: Severi
authors.forename: Wylie
authors.initials: W
authors.lastname: Vale
authors.forename: Mario
authors.initials: M
authors.lastname: Castellucci
authors.forename: Felice
authors.initials: F
authors.lastname: Petraglia
mesh_terms: D029404:Activin Receptors / Q000378:metabolism; D028341:Activins / Q000378:metabolism*; D000328:Adult; D015153:Blotting, Western; D004717:Endometrium / Q000473:pathology; D004815:Epidermal Growth Factor / Q000378:metabolism; D005260:Female; D038681:Follistatin / Q000378:metabolism; D038702:Follistatin-Related Proteins / Q000096:biosynthesis / Q000235:genetics; D058851:GPI-Linked Proteins; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007889:Leiomyoma / Q000378:metabolism* / Q000503:physiopathology; D008156:Luciferases / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism*; D055435:Myostatin / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D051906:Smad7 Protein / Q000378:metabolism; D013256:Steroids / Q000494:pharmacology*; D046509:Tissue Culture Techniques
chemical_list: D038681:Follistatin; D038702:Follistatin-Related Proteins; D058851:GPI-Linked Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D055435:Myostatin; D009363:Neoplasm Proteins; C497806:SMAD7 protein, human; D051906:Smad7 Protein; D013256:Steroids; C070636:TDGF1 protein, human; C422405:activin A; D028341:Activins; D004815:Epidermal Growth Factor; D012313:RNA; D008156:Luciferases; D029404:Activin Receptors