Effects of steroid hormone on estrogen sulfotransferase and on steroid sulfatase expression in endometriosis tissue and stromal cells

Effects of steroid hormone on estrogen sulfotransferase and on steroid sulfatase expression in endometriosis tissue and stromal cells
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DOI:
10.1016/j.jsbmb.2015.12.025
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发表时间:
2016-04-01
影响因子:
4.1
通讯作者:
Ferriani, Rui A.
Ferriani, Rui A.
中科院分区:
生物学2区
文献类型:
--
作者:
Piccinato, Carla A.;Neme, Rosa M.;Ferriani, Rui A.

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子宫内膜异位症是一种雌激素依赖性疾病,困扰着大约 10% 的育龄妇女,导致严重疼痛和不孕。研究了女性类固醇激素在调节关键雌激素代谢酶类固醇硫酸酯酶(STS)和雌激素磺基转移酶(SULT1E1)中的潜在作用。根据月经周期阶段比较浅层和深层子宫内膜异位病灶、子宫内膜异位症女性在位子宫内膜和对照患者子宫内膜的活检样本(n = 78)中STS和SULT1E1 mRNA的表达。在浅表和深层浸润病变中检测到 STS 基因表达增加,并且相对于浅表病变,在位子宫内膜中还观察到 SULT1E1 表达减少。此外,在子宫内膜异位症患者的活检标本中检测到 STS 和 SULT1E1 mRNA 表达水平之间存在显着的正相关性,而在对照个体中则没有。雌性类固醇激素对 SULT1E1 和 STS 表达的作用在子宫内膜异位症中得到了证实,这通过周期黄体期表达水平的增加得到了证实。用雌二醇和黄体酮处理的原代在位和异位子宫内膜基质细胞(代表黄体期,n = 3)中 STS 表达增加。尽管在体外激素诱导的子宫内膜基质细胞中观察到 STS mRNA 表达增加,但通过 LC-MS-MS 测量,激素治疗组之间从硫酸雌二醇形成雌二醇方面未检测到差异。有趣的是,在来自在位子宫内膜的基质细胞中观察到较高的STS表达,这与源自硫酸雌二醇的雌二醇形成一致。 STS 和 SULT1E1 的差异调节可以为 STS 抑制剂治疗用途的新研究提供见解。 (C) 2015 Elsevier Ltd. 保留所有权利。
Endometriosis is an estrogen-dependent disease that afflicts about 10% of women in their reproductive age, causing severe pain and infertility. The potential roles of female steroid hormones in modulating key estrogen-metabolizing enzymes, steroid sulfatase (STS) and estrogen sulfotransferase (SULT1E1), were investigated. The expression of STS and SULT1E1 mRNA in biopsy samples (n = 78) of superficial and deep endometriotic lesions, eutopic endometrium of women with endometriosis and endometrium from control patients were compared according to the menstrual cycle phase. Increased STS gene expression was detected in superficial and deep-infiltrating lesions and a reduced SULT1E1 expression was also observed in the eutopic endometrium relative to the superficial lesions. Additionally, a significantly positive correlation was detected between STS and SULT1E1 mRNA expression levels in biopsy specimens collected from the endometriosis patients, and not in control individuals. The actions of female steroid hormones on SULT1E1 and STS expression were evidenced in endometriosis, revealed by increased expression levels in the luteal phase of the cycle. There was an increased STS expression in primary eutopic and ectopic endometrial stromal cells treated with estradiol and progesterone (representative of the luteal phase, n = 3). Although an increased STS mRNA expression was observed in hormone-induced endometrial stromal cells in vitro, no difference could be detected between the hormone treatment groups in estradiol formation from estradiol sulfate measured by LC-MS-MS. Interestingly, a greater expression of STS was observed in stromal cells from eutopic endometrium with an agreement in estradiol formation originated from estradiol sulfate. The differential regulation of STS and SULT1E1 could provide insights for novel studies of the therapeutic use of STS inhibitors. (C) 2015 Elsevier Ltd. All rights reserved.