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.
Division of Obstetrics and Gynecology, Department of Molecular and Developmental Medicine, University of Siena, 'S. Maria alle Scotte', Siena, Italy.
Reprod Sci. 2014 Sep;21(9):1120-5. doi: 10.1177/1933719114542019. Epub 2014 Jul 6.
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.
子宫肌瘤是育龄妇女中最常见的良性妇科肿瘤，也是子宫切除术的单一最常见指征。有必要开发新的治疗方法来进行医学治疗，在这方面，正在研究几种激素药物。醋酸乌利司他（UPA；一种选择性孕激素受体调节剂）被认为是最有前途的药物之一，因为孕激素在子宫肌瘤的发生和生长中起着关键作用。甾体激素的作用部分是通过激活素 A 等生长因子介导的，激活素 A 增加细胞外基质的表达，促进子宫肌瘤的生长。本研究旨在测试 UPA 是否作用于子宫肌瘤细胞，从而影响激活素 A 系统的表达和功能。用 UPA 处理培养的子宫肌层和子宫肌瘤细胞，评估激活素 A（抑制素βA [INHBA]亚基）、其结合蛋白（卵泡抑素 [FST]和 FST 相关基因）及其受体（激活素受体样激酶 4 [ALK4]、激活素受体型 [ActR] II 和 ActRIIB）的信使 RNA（mRNA）表达水平。还研究了 UPA 对培养的子宫肌层和子宫肌瘤细胞中激活素 A 调节纤维连接蛋白和血管内皮生长因子 A（VEGF-A）mRNA 表达的影响。UPA 降低了培养的子宫肌瘤细胞中的 INHBA、FST、ActRIIB 和 Alk4 mRNA 表达。此外，UPA 能够阻断激活素 A 诱导的纤维连接蛋白或 VEGF-A mRNA 在子宫肌层和子宫肌瘤培养细胞中的表达增加。本数据表明，UPA 抑制子宫肌瘤细胞中激活素 A 的表达和功能，这可能代表该药物对子宫肌瘤的一种可能作用机制。
