Aromatase expression in endometriotic tissues and cell cultures of patients with endometriosis

Aromatase expression in endometriotic tissues and cell cultures of patients with endometriosis
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DOI:
10.1093/molehr/gal041
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发表时间:
2006-06-01
影响因子:
4
通讯作者:
Acien, P.
Acien, P.
中科院分区:
医学2区
文献类型:
--
作者:
Velasco, I.;Rueda, J.;Acien, P.

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细胞色素P-450芳香酶负责催化雄烯二酮转化为雌酮,因此其在子宫内膜异位组织中的表达可能有助于子宫内膜异位症的发生。本研究的目的一方面是确定在位和异位子宫内膜、健康腹膜、子宫肌层和子宫内膜异位症患者 (n = 12) 的在位和异位子宫内膜、子宫肌层和平滑肌瘤中是否存在芳香酶,另一方面确定腹膜液 (PF)、白介素 6 (IL-6) 和肿瘤坏死因子 α (TNF α) 对子宫内膜异位症的影响。来自子宫内膜异位基质细胞和皮下脂肪细胞的芳香酶活性。经过免疫组织化学分析,61%患者的子宫内膜异位组织中检测到芳香酶表达,而其余组织以及未患病女性的组织均为阴性。进行细胞培养以确定子宫内膜异位基质细胞和脂肪细胞中的芳香酶活性。添加 PF、TNF α,尤其是 IL-6(P < 0.05)可刺激两种细胞类型中观察到的基础酶活性。我们的研究结果证实了子宫内膜异位症中存在芳香酶,并且可能存在局部雌激素的产生,雌激素的产生可能受到某些因素(例如这些患者 PF 中存在的细胞因子)的刺激。因此,芳香酶抑制剂与免疫调节剂联合使用可能是未来临床试验中研究的一种新方法。
Cytochrome P-450 aromatase is responsible for catalysing the conversion of androstendione into estrone, so its expression in endometriotic tissue could contribute to the development of endometriosis. The aims of this study were, on the one hand, to determine the presence of aromatase in eutopic and ectopic endometrium, healthy peritoneum, myometrium and leiomyomas from patients with (n = 61) and without endometriosis (n = 12) and, on the other hand, to determine the effect of peritoneal fluid (PF), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF alpha) on aromatase activity from endometriotic stromal cells and subcutaneous adipocytes. After immunohistochemical analysis, aromatase expression was detected in the endometriotic tissue of 61% of patients, whereas the rest of the tissues, as well as those from disease-free women, were negative. Cell cultures were made to determine aromatase activity in endometriotic stromal cells and adipocytes. The addition of PF, TNF alpha and especially IL-6 (P < 0.05) stimulated the basal enzymatic activity observed in both cell types. Our findings confirm the presence of aromatase in endometriosis and probably the existence of a local estrogen production that may be stimulated by some factors such as cytokines present in the PF of these patients. Therefore, the use of aromatase inhibitors combined with immunomodulator agents could be a novel approach to be investigated in future clinical trials.