Division of Reproductive Biology Research, Northwestern University, Chicago, Illinois 60611, USA.
Fertil Steril. 2012 Jul;98(1):117-25. doi: 10.1016/j.fertnstert.2012.03.030. Epub 2012 Apr 21.
To define altered gene expression networks in endometriosis.
Experiments using endometriotic tissues and primary cells.
Division of Reproductive Biology Research, Northwestern University.
PATIENT(S): Premenopausal women.
INTERVENTION(S): Matched samples of eutopic endometrium and ovarian endometriosis (n = 8 patients) were analyzed by microarray and verified in a separate set of tissues (n = 6 patients). Experiments to define signaling pathways were performed in primary endometriotic stromal cells (n = 12 patients).
MAIN OUTCOMES MEASURE(S): Using a genome-wide in vivo approach, we identified 1,366 differentially expressed genes and a new gene network favoring increased glucocorticoid levels and action in endometriosis.
RESULT(S): Transcript and protein levels of 11β-hydroxysteroid dehydrogenase (HSD11B1), which produces cortisol, the biologically active glucocorticoid, were strikingly higher, whereas messenger RNA (mRNA) levels of the cortisol-degrading HSD11B2 enzyme were significantly lower in endometriotic tissue. Glucocorticoid receptor mRNA and protein levels were significantly higher in endometriosis. The inflammatory cytokine tumor necrosis factor robustly induced mRNA and protein levels of HSD11B1 and glucocorticoid receptor but suppressed HSD11B2 mRNA in primary endometriotic stromal cells, suggesting that tumor necrosis factor stimulates cortisol production and action. We also uncovered a subset of genes critical for prostaglandin synthesis and degradation, which favor high eicosanoid levels and activity in endometriosis.
CONCLUSION(S): The proinflammatory milieu of the endometriotic lesion stimulates cortisol synthesis and action in endometriotic lesions.
定义子宫内膜异位症中基因表达网络的改变。
使用子宫内膜异位症组织和原代细胞进行实验。
西北大学生殖生物学研究部。
绝经前妇女。
通过微阵列分析了 8 例患者的在位子宫内膜和卵巢子宫内膜异位症的匹配样本，并在另一组组织（n=6 例）中进行了验证。在原代子宫内膜间质细胞中进行了定义信号通路的实验（n=12 例）。
我们采用全基因组体内方法，鉴定了 1366 个差异表达基因和一个新的基因网络，该网络有利于增加子宫内膜异位症中的糖皮质激素水平和作用。
11β-羟类固醇脱氢酶（HSD11B1）的转录本和蛋白水平显著升高，HSD11B1 产生皮质醇，是生物活性糖皮质激素，而皮质醇降解酶 HSD11B2 的信使 RNA（mRNA）水平在子宫内膜异位症组织中显著降低。糖皮质激素受体 mRNA 和蛋白水平在子宫内膜异位症中显著升高。炎症细胞因子肿瘤坏死因子强烈诱导 HSD11B1 和糖皮质激素受体的 mRNA 和蛋白水平，但在原代子宫内膜间质细胞中抑制 HSD11B2 mRNA，表明肿瘤坏死因子刺激皮质醇的产生和作用。我们还发现了一组对前列腺素合成和降解至关重要的基因，它们有利于子宫内膜异位症中花生四烯酸水平和活性升高。
子宫内膜异位症病变中的促炎环境刺激了皮质醇在子宫内膜异位症病变中的合成和作用。
