Endometrial Intracrinology-Generation of an Estrogen-dominated Microenvironment in the Secretory Phase of Women

Endometrial Intracrinology-Generation of an Estrogen-dominated Microenvironment in the Secretory Phase of Women
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DOI:
10.1210/jc.2013-2140
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发表时间:
2013-11-01
影响因子:
5.8
通讯作者:
Saunders, P. T. K.
Saunders, P. T. K.
中科院分区:
医学2区
文献类型:
--
作者:
Gibson, D. A.;McInnes, K. J.;Saunders, P. T. K.

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背景:人类子宫内膜是一种复杂的多细胞组织,受卵巢源性类固醇激素周期性波动的影响。生育周期的特点是分化(蜕膜化)的子宫内膜基质细胞(ESC)hobbital:为了确定人类基质细胞蜕膜化的生物合成和分泌的estrogens.Setting的影响:一所大学的研究机构。没有妇女接受激素治疗或患有endometriosis.Main Outcome Measurements:mRNA和蛋白质编码的芳香化酶(CYP 19 A1)和3-β-羟基类固醇脱氢酶(HSD 3B 1)基因的表达进行了评估。芳香化酶活性测定使用氚水分析,类固醇代谢测定使用薄层色谱法。结果:蜕膜化诱导芳香化酶mRNA表达增加2倍,并与对照组比较,差异有统计学意义(P < 0. 05)。芳香化酶蛋白仅在蜕膜化ESC中检测到。3-β-羟基类固醇脱氢酶蛋白在蜕膜化前后均存在于ESC中;浓度似乎没有变化。证实了蜕膜化ESC中存在功能性芳香酶;当细胞与芳香酶抑制剂孵育时,E1和E2分泌到蜕膜化ESC的培养基中,并且浓度降低。结论:子宫内膜间质中芳香化酶的表达和活性增加,有利于E2主导的雌激素微环境的形成。
Context: The human endometrium is a complex multicellular tissue subject to cyclical fluctuations in ovarian-derived steroid hormones. Fertile cycles are characterized by differentiation (decidualization) of endometrial stromal cells (ESC).Objective: To determine the impact of human stromal cell decidualization on biosynthesis and secretion of estrogens.Setting: A University Research Institute.Patients: Primary ESC were derived from women with normal menstrual cycles (n = 12). None of the women were receiving hormonal therapy or suffering from endometriosis.Main Outcome Measurements: Expression of mRNA and protein encoded by the aromatase (CYP19A1) and 3-beta-hydroxysteroid dehydrogenase (HSD3B1) genes was assessed. Aromatase activity was measured using a tritiated water assay; steroid metabolism was determined using thin layer chromatography. Estrone (E1) andestradiol (E2) in cell culturemediaweremeasuredby ELISA.Results: Decidualization induced a two-fold increase in aromatase mRNA. Aromatase protein was only detected in decidualized ESC. 3-beta-Hydroxysteroid dehydrogenase protein was present in ESC both before and after decidualization; concentrations appeared unchanged. The existence of functional aromatase in decidualized ESC was confirmed; E1 and E2 were secreted into culture media in decidualized ESC and concentrations were reduced when cells were incubated with an aromatase inhibitor. Decidualization resulted in reduced metabolism of E2 and an increase in the ratio of E2: E1.Conclusions: Decidualization is characterized by an increase in aromatase expression/ activity favoring the generation of an E2-dominated estrogen microenvironment within the endometrial stroma.