| Literature DB >> 20104427 |
Serdar E Bulun1, You-Hong Cheng, Mary Ellen Pavone, Qing Xue, Erkut Attar, Elena Trukhacheva, Hideki Tokunaga, Hiroki Utsunomiya, Ping Yin, Xia Luo, Zhihong Lin, Gonca Imir, Stephen Thung, Emily J Su, J Julie Kim.
Abstract
Loss of progesterone signaling in the endometrium may be a causal factor in the development of endometriosis, and progesterone resistance is commonly observed in women with this disease. In endometriotic stromal cells, the levels of progesterone receptor (PR), particularly the PR-B isoform, are significantly decreased, leading to a loss of paracrine signaling. PR deficiency likely underlies the development of progesterone resistance in women with endometriosis who no longer respond to progestin therapy. Here we review the complex epigenetic and transcriptional mechanisms leading to PR deficiency. The initial event may involve deficient methylation of the estrogen receptor (ER)beta promoter resulting in pathologic overexpression of ERbeta in endometriotic stromal cells. We speculate that alterations in the relative levels of ERbeta and ERalpha in endometrial tissue dictate E2-regulated PR expression, such that a decreased ERalpha-tauomicron-ERbeta ratio may result in suppression of PR. In this review, we propose a molecular model that may be responsible for changes in ERbeta and ERalpha leading to PR loss and progesterone resistance in endometriosis.Entities:
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Year: 2010 PMID： 20104427 PMCID： PMC3073375 DOI： 10.1055/s-0029-1242991
Source DB: PubMed Journal: Semin Reprod Med ISSN： 1526-4564 Impact factor: 1.303