BACKGROUND Previous studies of expression profiles of major endometrial effectors of steroid physiology in endometriosis have yielded markedly conflicting conclusions, presumably because the relative effects of type of endometriosis, fertility history and menstrual cycle phases on the measured variables were not considered. In the present study, endometrial mRNA and protein levels of several effectors of steroid biosynthesis and action in patients with stage III-IV ovarian endometriosis (OE) with known fertility and menstrual cycle histories were compared with the levels in control endometrium to test this concept. METHODS Endometrial samples were collected from patients without endometriosis (n = 32) or OE stages III-IV (n = 52) with known fertility and cycle histories. qRT-PCR and immunoblotting experiments were performed to measure levels of NR5A1, STAR, CYP19A1, HSD17Bs, ESRs and PGR transcripts and proteins, respectively. Tissue concentrations of steroids (P4, T, E1 and E2) were measured using ELISAs. RESULTS The levels of expression of aromatase and ERβ were lower (P < 0.0001) and 17β-HSD1 (P < 0.0001) and PRA (P < 0.01) were higher in OE endometrium. Lower aromatase levels and higher 17β-HSD1 levels were detected in fertile (aromatase: P < 0.05; 17β-HSD1: P < 0.0001) and infertile (aromatase: P < 0.0001; 17β-HSD1: P < 0.0001) OE endometrium than in the matched control tissues. Both proliferative (PP) and secretory (SP) phase OE samples expressed aromatase (P < 0.0001) and ERβ (PP: P < 0.001; SP: P < 0.01) at lower levels and 17β-HSD1 (P < 0.0001) and PRA (PP: P < 0.01; SP: P < 0.0001) at higher levels than matched controls. Higher 17β-HSD1 (P < 0.01) and E2 (P < 0.05) levels and a lower (P < 0.01) PRB/PRA ratio was observed in infertile secretory phase OE endometrium than in control. CONCLUSIONS We report that dysregulated expression of 17β-HSD1 and PGR resulting in hyperestrogenism and progesterone resistance during the secretory phase of the menstrual cycle, rather than an anomaly in aromatase expression, was the hallmark of eutopic endometrium from infertile OE patients. Furthermore, the results provide proof of concept that the fertility and menstrual cycle histories exerted relatively different effects on steroid physiology in the endometrium from OE patients compared with the control subjects.

中文翻译：

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对中度至重度卵巢子宫内膜异位症患者在位子宫内膜中类固醇代谢酶和类固醇受体多因素分布的评估。

背景技术以前对子宫内膜异位症中类固醇生理学的主要子宫内膜效应子表达谱的研究得出了明显矛盾的结论，大概是因为未考虑子宫内膜异位症的类型，生育史和月经周期阶段对测量变量的相对影响。在本研究中，将具有已知生育能力和月经周期历史的III-IV期卵巢子宫内膜异位症（OE）患者的类固醇生物合成和作用的几种效应子的子宫内膜mRNA和蛋白水平与对照子宫内膜中的水平进行比较，以检验这一概念。方法从子宫内膜异位症（n = 32）或OE阶段III-IV（n = 52），具有已知的生育力和周期史的患者中收集子宫内膜样品。进行了qRT-PCR和免疫印迹实验，分别测量了NR5A1，STAR，CYP19A1，HSD17B，ESR和PGR转录本和蛋白质的水平。使用ELISA测量类固醇的组织浓度（P4，T，E1和E2）。结果OE子宫内膜中芳香化酶和ERβ的表达水平较低（P <0.0001），而17β-HSD1（P <0.0001）和PRA（P <0.01）则较高。在可育（芳香化酶：P <0.05；17β-HSD1：P <0.0001）和不育（芳香化酶：P <0.0001；17β-HSD1：P <0.0001）OE子宫内膜中检测到较低的芳香化酶水平和较高的17β-HSD1水平。匹配的对照组织。增殖（PP）和分泌（SP）期OE样品均以较低水平表达芳香酶（P <0.0001）和ERβ（PP：P <0.001; SP：P <0.01）和17β-HSD1（P <0.0001）和PRA（ PP：P <0.01；SP：P <0.0001）的水平高于匹配的对照组。与对照组相比，在不育分泌期OE子宫内膜中观察到较高的17β-HSD1（P <0.01）和E2（P <0.05）水平，较低的PRB / PRA比（P <0.01）。结论我们报告说，在月经周期的分泌期，表达异常的17β-HSD1和PGR导致雌激素过多和孕酮抵抗，而不是芳香酶表达异常，是不育OE患者子宫内膜异位症的标志。此外，该结果提供了概念上的证明，即与对照组相比，生育能力和月经周期史对OE患者子宫内膜中的类固醇生理产生了相对不同的影响。不育分泌期OE子宫内膜中PRB / PRA的含量降低了0.05），PRB / PRA的比例也低于对照。结论我们报告说，在月经周期的分泌期，表达异常的17β-HSD1和PGR导致雌激素过多和孕酮抵抗，而不是芳香酶表达异常，是不育OE患者子宫内膜异位症的标志。此外，该结果提供了概念上的证明，即与对照组相比，生育能力和月经周期史对OE患者子宫内膜中的类固醇生理产生了相对不同的影响。不育分泌期OE子宫内膜中PRB / PRA的含量降低了0.05），PRB / PRA的比例也低于对照。结论我们报告说，在月经周期的分泌期，表达异常的17β-HSD1和PGR导致雌激素过多和孕酮抵抗，而不是芳香酶表达异常，是不育OE患者子宫内膜异位症的标志。此外，该结果提供了概念上的证明，即与对照组相比，生育能力和月经周期史对OE患者子宫内膜中的类固醇生理产生了相对不同的影响。结论我们报告说，在月经周期的分泌期，表达异常的17β-HSD1和PGR导致雌激素过多和孕酮抵抗，而不是芳香酶表达异常，是不育OE患者子宫内膜异位症的标志。此外，该结果提供了概念上的证明，即与对照组相比，生育能力和月经周期史对OE患者子宫内膜中的类固醇生理产生了相对不同的影响。结论我们报告说，在月经周期的分泌期，表达异常的17β-HSD1和PGR导致雌激素过多和孕酮抵抗，而不是芳香酶表达异常，是不育OE患者子宫内膜异位症的标志。此外，该结果提供了概念上的证明，即与对照组相比，生育能力和月经周期史对OE患者子宫内膜中的类固醇生理产生了相对不同的影响。