Piccinato Carla A, Neme Rosa M, Torres Natália, Sanches Lívia Renta, Derogis Priscilla Bento Mattos Cruz, Brudniewski Heloísa F, Rosa E Silva Júlio C, Ferriani Rui A
Hospital Israelita Albert Einstein, São Paulo, SP 05652-900, Brazil; Department of Gynaecology and Obstetrics, School of Medicine of Ribeirão Preto, Universidade de São Paulo, Brazil.
Hospital Israelita Albert Einstein, São Paulo, SP 05652-900, Brazil; Centro de Endometriose São Paulo, Av. República do Líbano, 460 São Paulo, SP 04502-000, Brazil.
J Steroid Biochem Mol Biol. 2016 Apr;158:117-126. doi: 10.1016/j.jsbmb.2015.12.025. Epub 2015 Dec 23.
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.
子宫内膜异位症是一种雌激素依赖性疾病，影响约10%的育龄妇女，会导致严重疼痛和不孕。研究了女性甾体激素在调节关键雌激素代谢酶——类固醇硫酸酯酶（STS）和雌激素硫酸转移酶（SULT1E1）方面的潜在作用。根据月经周期阶段，比较了浅表和深部子宫内膜异位病变活检样本（n = 78）、子宫内膜异位症女性的在位内膜以及对照患者内膜中STS和SULT1E1 mRNA的表达。在浅表和深部浸润性病变中检测到STS基因表达增加，相对于浅表病变，在位内膜中SULT1E1表达也降低。此外，在子宫内膜异位症患者而非对照个体采集的活检标本中，检测到STS和SULT1E1 mRNA表达水平之间存在显著正相关。女性甾体激素对SULT1E1和STS表达的作用在子宫内膜异位症中得到证实，表现为周期黄体期表达水平升高。在用雌二醇和孕酮处理的原发性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。虽然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，但通过液相色谱-串联质谱法测定，激素处理组之间在硫酸雌二醇形成雌二醇方面未检测到差异。有趣的是，在位内膜基质细胞中观察到更高的STS表达，且在硫酸雌二醇产生雌二醇方面具有一致性。STS和SULT1E1的差异调节可为STS抑制剂治疗用途的新研究提供思路。
