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Progesterone's role in deep infiltrating endometriosis: Progesterone receptor and estrogen metabolism enzymes expression and physiological changes in primary endometrial stromal cell culture.
Molecular and Cellular Endocrinology ( IF 3.8 ) Pub Date : 2020-01-28 , DOI: 10.1016/j.mce.2020.110743
Gil Kamergorodsky 1 , Adriana L Invitti 2 , Paulo D'Amora 2 , Rafael M Parreira 2 , Alexander Kopelman 3 , Tatiana C S Bonetti 2 , Manoel J B C Girão 4 , Eduardo Schor 1
Affiliation  

To study progesterone signaling activation, we measured changes in extracellular pH as a reflection of Na+/H+ exchange (NHE) using a cytosensor microphysiometer and assessed progesterone receptor (PR) and estrogen metabolism enzymes mRNA expression in cultured endometrial cells from women with deep infiltrating endometriosis and healthy controls using real-time quantitative PCR. This study was conducted at a University hospital and included patients with and without deep infiltrating endometriosis (DIE). Primary endometrial stromal cells (ECs) from women with DIE and controls were treated with 17β-estradiol and progesterone prior to microphysiometer measurements and qPCR evaluations. Decreased progesterone responsiveness and decreased total nuclear PR and HSD17B1 mRNA expression were observed in cultured ECs from women with deep infiltrating endometriosis relative to those from control samples before and after hormone treatment. These cells also showed increased 17β-hydroxysteroid dehydrogenases types 2 (HSD17B2) relative to control group and increased expression of aromatase (CYP19) after exposure to progesterone. These physiological and expression patterns observed in ECs cultures from women with DIE reinforces previous findings in the literature supporting the progesterone resistance hypothesis in the pathogenesis of endometriosis.

中文翻译:

孕酮在深度浸润性子宫内膜异位症中的作用:子宫内膜基质细胞培养中孕酮受体和雌激素代谢酶的表达及生理变化。

为了研究孕激素信号激活,我们使用细胞传感器显微生理仪测量了细胞外pH的变化,以反映Na + / H +交换(NHE),并评估了深浸润型子宫内膜异位症妇女培养的子宫内膜细胞中的孕酮受体(PR)和雌激素代谢酶mRNA表达。使用实时定量PCR的健康对照。这项研究是在一家大学医院进行的,包括有或没有深层浸润性子宫内膜异位症(DIE)的患者。在进行微生理仪测量和qPCR评估之前,将患有DIE的女性和对照组的原代子宫内膜基质细胞(ECs)用17β-雌二醇和孕酮处理。与激素治疗前后的对照样品相比,深浸润型子宫内膜异位症妇女的培养的EC中孕酮反应性降低,总核PR和HSD17B1 mRNA表达降低。这些细胞还显示出相对于对照组增加的17β-羟类固醇脱氢酶2型(HSD17B2)和暴露于孕激素后的芳香化酶(CYP19)表达增加。在患有DIE的女性的ECs文化中观察到的这些生理和表达模式加强了以前文献的发现,这些文献支持子宫内膜异位症发病机理中的孕酮抗性假设。这些细胞还显示出相对于对照组增加的17β-羟类固醇脱氢酶2型(HSD17B2)和暴露于孕激素后的芳香化酶(CYP19)表达增加。在患有DIE的女性的ECs文化中观察到的这些生理和表达模式加强了以前文献的发现,这些文献支持子宫内膜异位症发病机理中的孕酮抗性假设。这些细胞还显示出相对于对照组增加的17β-羟类固醇脱氢酶2型(HSD17B2)和暴露于孕激素后的芳香化酶(CYP19)表达增加。在患有DIE的女性的ECs文化中观察到的这些生理和表达模式加强了以前文献的发现,这些文献支持子宫内膜异位症发病机理中的孕酮抗性假设。
更新日期:2020-01-30
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