Aromatase expression in endometriosis.
Aromatase expression in endometriosis.
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DOI：
10.1210/jcem.81.1.8550748
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发表时间：
1996
期刊：
影响因子：
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通讯作者：
L. Noble;E. Simpson;A. Johns;S. Bulun
中科院分区：
文献类型：
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作者：
L. Noble;E. Simpson;A. Johns;S. Bulun
C19类固醇转化为雌激素发生在许多组织中，如卵巢和胎盘，并由芳香化酶P450 （P450arom； CYP19基因的产物）催化。P450arom在许多子宫肿瘤如平滑肌瘤和子宫内膜癌中也有表达。另一方面，P450arom在正常子宫内膜和子宫肌组织中未检测到表达。本研究旨在确定在子宫内膜异位症患者的腹膜子宫内膜异位症植入物和异位子宫内膜中芳香化酶表达的存在与否。对14例经组织学证实的盆腔子宫内膜异位症患者在腹腔镜或开腹手术时行盆腔腹膜子宫内膜异位症植入物（n = 17，如后腔、膀胱和前腔）和异位子宫内膜切开术（n = 11）。盆腔腹膜活检远端子宫内膜异位症植入物和正常子宫内膜组织（n = 7）从无疾病的妇女被用作阴性对照。我们使用竞争性RT-PCR技术，采用内部标准扩增从这些组织中分离的总核糖核酸（RNA）中的p450 - arom转录本。在所有子宫内膜异位症植入物和子宫内膜异位症患者的所有异位子宫内膜组织中均检测到P450arom转录本。在无疾病妇女的子宫内膜组织或无子宫内膜异位症的腹膜组织中未检测到P450arom信使RNA种类。在涉及前腹壁全厚度的子宫内膜异位症植入物中检测到最高水平的转录本。子宫内膜异位症肿块中心的P450arom转录水平是周围脂肪组织的4倍。最近有研究表明，芳香化酶在各种人体组织中的表达是由组织特异性启动子通过选择性剪接来调节的。为了分析启动子的使用情况，我们通过RT-PCR扩增了2个子宫内膜异位症植入物中P450arom转录本中最可能的启动子特异性未翻译的5'端。这些子宫内膜异位症植入物似乎同时使用脂肪型启动子I.4和性腺型启动子II来表达芳香酶。在脂肪组织中，启动子I.4用于芳香化酶的表达最近被观察到受白细胞介素-6 （IL-6）细胞因子家族成员的调节。基于这些发现，我们通过RT-PCR检测了5个子宫内膜异位症组织和1个异位子宫内膜样本中IL-6和IL-11信使RNA的表达。我们在所有子宫内膜异位症组织和异位子宫内膜组织样本中检测到IL-6和IL-11转录物。我们的研究结果表明，子宫内膜异位症患者的异位子宫内膜组织和子宫内膜异位症植入物与无病女性的正常子宫内膜组织在生化方面存在差异。芳香化酶在子宫内膜异位症患者异位子宫内膜组织中的表达可能与这些组织在腹膜表面着床的能力有关。此外，这些植入物中雌激素的产生可能有助于促进它们的生长。这些组织中IL-6和IL-11表达的增加表明P450arom在子宫内膜异位症中的表达可能部分受到这些细胞因子的调节。
The conversion of C19 steroids to estrogens occurs in a number of tissues, such as the ovary and placenta, and is catalyzed by aromatase P450 (P450arom; the product of the CYP19 gene). P450arom expression has also been detected in a number of uterine tumors, such as leiomyomas and endometrial cancer. On the other hand, P450arom expression was undetectable in normal endometrial and myometrial tissues. The present study was conducted to determine the presence or absence of aromatase expression in peritoneal endometriotic implants and in the eutopic endometrium of women with endometriosis. Endometriotic implants in pelvic peritoneum (n = 17; e.g. posterior culdesac, bladder, and anterior culdesac) and eutopic endometrial curettings (n = 11) of 14 patients with histologically documented pelvic endometriosis were obtained at the time of laparoscopy or laparotomy. Pelvic peritoneal biopsies distal to endometriotic implants as well as normal endometrial tissues (n = 7) from disease-free women were used as negative controls. We used competitive RT-PCR technology employing an internal standard to amplify P450arom transcripts in total ribonucleic acid (RNA) isolated from these tissues. P450arom transcripts were detected in all endometriotic implants and in all eutopic endometrial tissues from patients with endometriosis. P450arom messenger RNA species were not detectable in endometrial tissues from disease-free women or in endometriosis-free peritoneal tissues. The highest levels of transcripts were detected in an endometriotic implant that involved the full thickness of the anterior abdominal wall. The P450arom transcript level within the core of this endometriotic mass was 4-fold higher than that in the surrounding adipose tissue. It has been shown recently that aromatase expression in various human tissues is regulated by the use of tissue-specific promoters via alternative splicing. To analyze promoter usage, we amplified by RT-PCR the most likely promoter-specific untranslated 5'-termini of P450arom transcripts in 2 endometriotic implants. It appears that these endometriotic implants use both the adipose-type promoter I.4 and gonadal-type promoter II for aromatase expression. The use of promoter I.4 for aromatase expression in adipose tissue has been recently observed to be regulated by members of the interleukin-6 (IL-6) cytokine family. Based on these findings, we examined by RT-PCR, IL-6 and IL-11 messenger RNA expression in 5 endometriotic tissues and 1 eutopic endometrial sample from a patient with endometriosis. We detected IL-6 and IL-11 transcripts in all endometriotic tissues and in the eutopic endometrial tissue sample studied. Our findings indicate that both eutopic endometrial tissues and endometriotic implants from patients with endometriosis are biochemically different from normal endometrial tissues of disease-free women. The presence of aromatase expression in eutopic endometrial tissues from patients with endometriosis may be related to the capability of implantation of these tissues on peritoneal surfaces. Furthermore, the possibility of estrogen production in these implants may serve to promote their growth. Increased IL-6 and IL-11 expression in these tissues suggests that P450arom expression in endometriosis may be regulated in part by these cytokines.