title: Ulipristal acetate modulates the expression and functions of activin a in leiomyoma cells.
abstract: Uterine leiomyoma is the most common benign gynecological tumor in women of reproductive age and represents the single most common indication for hysterectomy. A development of new treatments is necessary for a medical management, and in this direction, several hormonal drugs are under investigation. Ulipristal acetate (UPA; a selective progesterone receptor modulator) is considered as one of the most promising because progesterone has a critical role in development and growth of uterine leiomyoma. The effect of steroids is partly mediated by growth factors like activin A which increases extracellular matrix expression contributing to the growth of leiomyoma. The present study aimed to test whether UPA acts on leiomyoma cells affecting expression and functions of activin A system. Cultured myometrial and leiomyoma cells were treated with UPA, and messenger RNA (mRNA) expression levels of activin A (inhibin βA [INHBA] subunits), its binding proteins (follistatin [FST] and FST-related gene), and its receptors (activin receptor-like kinase 4 [ALK4], activin receptor type [ActR] II, and ActRIIB) were evaluated. The effect of UPA on activin A modulation of fibronectin and vascular endothelial growth factor A (VEGF-A) mRNA expression in cultured myometrial and leiomyoma cells was also studied. Ulipristal acetate decreased INHBA, FST, ActRIIB, and Alk4 mRNA expressions in leiomyoma cultured cells. In addition, UPA was able to block the activin A-induced increase in fibronectin or VEGF-A mRNA expression in myometrial and in leiomyoma cultured cells. The present data show that UPA inhibits activin A expression and functions in leiomyoma cells, and this may represent a possible mechanism of action of the drug on uterine leiomyoma.
authors.affiliation: Department of Experimental and Clinical Medicine, Faculty of Medicine, Polytechnic University of Marche, Ancona, Italy Department of Information Engineering, Polytechnic University of Marche, Ancona, Italy.
authors.forename: Pasquapina
authors.initials: P
authors.lastname: Ciarmela
authors.affiliation: Division of Obstetrics and Gynecology, Department of Molecular and Developmental Medicine, University of Siena, 'S. Maria alle Scotte', Siena, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Carrarelli
authors.affiliation: Department of Experimental and Clinical Medicine, Faculty of Medicine, Polytechnic University of Marche, Ancona, Italy Department of Botany, Biotechnology and Microbiology Laboratory, University of Rajshahi, Rajshahi, Bangladesh.
authors.forename: Md Soriful
authors.initials: MS
authors.lastname: Islam
authors.affiliation: Department of Experimental and Clinical Medicine, Faculty of Medicine, Polytechnic University of Marche, Ancona, Italy.
authors.forename: Milijana
authors.initials: M
authors.lastname: Janjusevic
authors.affiliation: Division of Obstetrics and Gynecology, Department of Molecular and Developmental Medicine, University of Siena, 'S. Maria alle Scotte', Siena, Italy.
authors.forename: Errico
authors.initials: E
authors.lastname: Zupi
authors.affiliation: Division of Obstetrics and Gynecology, Department of Molecular and Developmental Medicine, University of Siena, 'S. Maria alle Scotte', Siena, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Tosti
authors.affiliation: Department of Experimental and Clinical Medicine, Faculty of Medicine, Polytechnic University of Marche, Ancona, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Castellucci
authors.affiliation: Division of Obstetrics and Gynecology, Department of Molecular and Developmental Medicine, University of Siena, 'S. Maria alle Scotte', Siena, Italy felice.petraglia@unisi.it.
authors.forename: Felice
authors.initials: F
authors.lastname: Petraglia
mesh_terms: D028341:Activins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000502:physiology; D000328:Adult; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007889:Leiomyoma / Q000188:drug therapy / Q000378:metabolism*; D008875:Middle Aged; D009649:Norpregnadienes / Q000494:pharmacology* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D009649:Norpregnadienes; C422405:activin A; D028341:Activins; C555622:ulipristal acetate
keywords: VEGF-A; activin; activin receptors; fibronectin; follistatin; ulipristal acetate; uterine fibroids; uterine leiomyoma