Progesterone receptor isoform A but not B is expressed in endometriosis
Progesterone receptor isoform A but not B is expressed in endometriosis
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DOI：
10.1210/jc.85.8.2897
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发表时间：
2000-08-01
影响因子：
5.8
通讯作者：
Bulun, SE
中科院分区：
文献类型：
--
作者：
Attia, GR;Zeitoun, K;Bulun, SE
我们以前证明，17 β羟类固醇脱氢酶2型，酶的失活雌二醇雌酮，表达在黄体在位子宫内膜的孕酮反应，但不同时活检腹膜增生组织。孕酮抵抗的分子证据，以及子宫内膜异位症对孕酮治疗抵抗的临床观察，使我们确定了在位子宫内膜和卵巢外增生组织中孕酮受体（PR）亚型PR-A和PR-B的水平。有人提出孕酮作用于靶基因主要是由PR-B的同源二聚体介导的，而截短的变体PR-A充当PR-B功能的阻遏物。免疫沉淀，然后通过Western印迹分析，进行检测PR-A和PR-B的特异性条带在配对样本的异位和在位子宫内膜组织同时活检从18名妇女接受腹腔镜检查在月经周期的各个阶段。PR-B存在于18个在位子宫内膜样本中的17个中，并且其水平在排卵前阶段增加，预期，而PR-A在所有样本（n = 18）中检测到，其水平具有相似但不太突出的周期变化。然而，在子宫内膜异位样本中，没有可检测到的PR-B，而PR-A在所有样本（n = 18）中均被检测到，尽管与在位子宫内膜相比，PR-A的水平要低得多，并且没有任何周期性变化。PR-A和PR-B在异位和在位子宫内膜组织中的水平被测定，并在标准化为总蛋白和雌激素受体-cr水平后进行比较。使用RNase保护试验，我们还间接证明了只有PR-A转录本存在于子宫内膜异位组织样本（n = 8），而PR-A和PR-B转录本在所有在位子宫内膜样本（n = 8）中都很容易检测到。这表明，未能检测到的PR-E蛋白在增生组织中是由于PR-B转录本的缺乏。我们的结论是，从实验室和临床观察，孕激素抵抗在卵巢组织可能占抑制性PR亚型PR-A的存在和刺激性亚型PR-B的情况下。
We previously demonstrated that 17 beta hydroxysteroid dehydrogenase type 2, the enzyme that inactivates estradiol to estrone, is expressed in luteal eutopic endometrium in response to progesterone but not in simultaneously biopsied peritoneal endometriotic tissue. This molecular evidence of progesterone resistance, together with the clinical observation of resistance of endometriosis to treatment with progestins, led us to determine the levels of progesterone receptor (PR) isoforms PR-A and PR-B in eutopic endometrial and extra-ovarian endometriotic tissues. It was proposed that progesterone action on target genes is mediated primarily by homodimers of PR-B, whereas the truncated variant PR-A acts as a repressor of PR-B function. Immunoprecipitation, followed by Western blot analysis, was performed to detect bands specific for PR-A and PR-B in paired samples of endometriotic and eutopic endometrial tissues simultaneously biopsed from 18 women undergoing laparoscopy during various phases of the menstrual cycle. PR-B was present in 17 of 18 eutopic endometrial samples, and its level increased in the preovulatory phase, expected, whereas PR-A was detected in all samples (n = 18) with a similar, but less prominent, cyclic variation in its levels. In endometriotic samples, however, no detectable PR-B could be demonstrated, whereas PR-A was detected in all samples (n = 18), albeit in much lower levels and without any cyclic variation in contrast with the eutopic endometrium. Levels of PR-A and PR-B in endometriotic and eutopic endometrial tissues were determined and compared after normalization to total protein and estrogen receptor-cr levels. Using RNase protection assay, we also demonstrated indirectly that only PR-A transcripts were present in endometriotic tissue samples (n = 8), whereas both PR-A and PR-B transcripts were readily detectable in all eutopic endometrial samples (n = 8). This was indicative that failure to detect PR-E protein in endometriotic tissues is due to the absence of PR-B transcripts. We conclude that progesterone resistance in endometriotic tissue from laboratory and clinical observations may be accounted for by the presence of the inhibitory PR isoform PR-A and the absence of the stimulatory isoform PR-B.