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: Pasquapina Ciarmela, Patrizia Carrarelli, Md Soriful Islam, Milijana Janjusevic, Errico Zupi, Claudia Tosti, Mario Castellucci, Felice Petraglia
• Journal: Reproductive sciences (Thousand Oaks, Calif.) (Reprod Sci) Vol. 21 Issue 9 Pg. 1120-5 (Sep 2014) ISSN: 1933-7205 [Electronic] United States
• PMID: 25001022 (Publication Type: Journal Article)
• Copyright: © The Author(s) 2014.

Chemical References

• Norpregnadienes
• activin A
• Activins
• ulipristal acetate

Topics

• Activins (antagonists & inhibitors, biosynthesis, physiology)
• Adult
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Leiomyoma (drug therapy, metabolism)
• Middle Aged
• Norpregnadienes (pharmacology, therapeutic use)
• Tumor Cells, Cultured
• Uterine Neoplasms (drug therapy, metabolism)