title: Myostatin, follistatin and activin type II receptors are highly expressed in adenomyosis.
abstract: OBJECTIVE
  To evaluate the expression pattern of activins and related growth factor messenger RNA (mRNA) levels in adenomyotic nodules and in their endometrium.
  
  
  METHODS
  Prospective study.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  Symptomatic premenopausal women scheduled to undergo hysterectomy for adenomyosis.
  
  
  METHODS
  Samples from adenomyotic nodules and homologous endometria were collected. Endometrial tissue was also obtained from a control group.
  
  
  METHODS
  Quantitative real-time polymerase chain reaction (PCR) analysis and immunohistochemical localization of activin-related growth factors (activin A, activin B, and myostatin), binding protein (follistatin), antagonists (inhibin-α, cripto), and receptors (ActRIIa, ActRIIb) were performed.
  
  
  RESULTS
  Myostatin mRNA levels in adenomyotic nodule were higher than in eutopic endometrium and myostatin, activin A, and follistatin concentrations were higher than in control endometrium. No difference was observed for inhibin-α, activin B, and cripto mRNA levels. Increased mRNA levels of ActRIIa and ActRIIb were observed in adenomyotic nodules compared with eutopic endometrium and control endometrium. Immunofluorescent staining for myostatin and follistatin confirmed higher protein expression in both glands and stroma of patients with adenomyosis than in controls.
  
  
  CONCLUSIONS
  The present study showed for the first time that adenomyotic tissues express high levels of myostatin, follistatin, and activin A (growth factors involved in proliferation, apoptosis, and angiogenesis). Increased expression of their receptors supports the hypothesis of a possible local effect of these growth factors in adenomyosis. The augmented expression of ActRIIa, ActRIIb, and follistatin in the endometrium of these patients may play a role in adenomyosis-related infertility.
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Carrarelli
authors.affiliation: Department of Obstetrics and Gynaecology, Chang Gung Memorial Hospital at Linkou and Chang Gung University College of Medicine, Taoyuan, Taiwan; Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Chih-Fen
authors.initials: CF
authors.lastname: Yen
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Felice
authors.initials: F
authors.lastname: Arcuri
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Funghi
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Tosti
authors.affiliation: Department of Obstetrics and Gynaecology, Chang Gung Memorial Hospital at Linkou and Chang Gung University College of Medicine, Taoyuan, Taiwan; Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Tzu-Hao
authors.initials: TH
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynaecology, The Ohio State University College of Medicine, Columbus, Ohio.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Huang
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy. Electronic address: felice.petraglia@unisi.it.
authors.forename: Felice
authors.initials: F
authors.lastname: Petraglia
mesh_terms: D030301:Activin Receptors, Type II / Q000032:analysis* / Q000235:genetics; D028341:Activins / Q000032:analysis; D062788:Adenomyosis / Q000235:genetics / Q000378:metabolism* / Q000601:surgery; D000328:Adult; D016022:Case-Control Studies; D004717:Endometrium / Q000737:chemistry* / Q000601:surgery; D005260:Female; D038681:Follistatin / Q000032:analysis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D055435:Myostatin / Q000032:analysis* / Q000235:genetics; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C503233:FST protein, human; D038681:Follistatin; C525911:MSTN protein, human; D055435:Myostatin; D012333:RNA, Messenger; C422405:activin A; D028341:Activins; C579679:ACVR2B protein, human; D030301:Activin Receptors, Type II; C425585:activin receptor type II-A
keywords: Adenomyosis; activin; activin receptors; crypto; eutopic endometrium; follistatin; infertility; inhibin; myostatin; nodular adenomyosis