Altered Gene Expression Profile in Vaginal Polypoid Endometriosis Resembles Peritoneal Endometriosis and Is Consistent with Increased Local Estrogen Production

Department of Obstetrics, Gynecology and Women's Health, University of Missouri School of Medicine, Columbia, MO 65212, USA.
Gynecologic and Obstetric Investigation (Impact Factor: 1.7). 12/2010; 71(2):77-86. DOI: 10.1159/000320736
Source: PubMed


In a university hospital setting, a 25-year-old woman presented with large vaginal and cervical polyps. Past medical history was significant for stage IV endometriosis. Polypectomy was performed and the polyps were histologically consistent with endometriosis. Gene expression was compared with control vaginal tissue to assess if the altered gene expression profile was similar to peritoneal endometriosis.
Using quantitative reverse transcription, real-time PCR, estrogen receptor-β expression was found to be upregulated 10-fold while estrogen receptor-α expression was downregulated 5-fold in the vaginal polyp relative to control vaginal tissue. The estrogen-synthesizing enzyme aromatase was upregulated 8-fold and 3β-hydroxysteroid dehydrogenase was upregulated 400-fold in the polyp. Immunohistochemical staining revealed altered cell type localization for progesterone receptor in the polyp and increased cell proliferation in polyp stromal cells relative to control.
Increased proliferation in the vaginal polypoid endometriotic tissue may be due to increased local estrogen production. The altered gene expression profile was very similar to the altered gene expression profile seen in peritoneal endometriosis.

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    ABSTRACT: Immune-endocrine interplay may play a major role in the pathogenesis of endometriosis. In the present study, we have investigated the interaction between macrophage migration inhibitory factor (MIF), a major pro-inflammatory and growth-promoting factor markedly expressed in active endometriotic lesions, and estradiol (E(2)) in ectopic endometrial cells. Our data showed a significant increase of MIF protein secretion and mRNA expression in endometriotic cells in response to E(2). MIF production was blocked by Fulvestrant, an estrogen receptor (ER) antagonist, and induced by ERα and ERβ selective agonists propyl-pyrazole-triol (PPT) and diarylpropionrile (DPN), respectively, thus demonstrating a specific receptor-mediated effect. Cell transfection with MIF promoter construct showed that E(2) significantly stimulates MIF promoter activity. Interestingly, our data further revealed that MIF reciprocally stimulates aromatase protein and mRNA expression via a posttranscriptional mRNA stabilization mechanism, that E(2) itself can upregulate aromatase expression, and that inhibition of endogenous MIF, using MIF specific siRNA, significantly inhibits E(2)-induced aromatase. Thus, the present study revealed the existence of a local positive feedback loop by which estrogen acts directly on ectopic endometrial cells to upregulate the expression of MIF, which, in turn, displays the capability of inducing the expression of aromatase, the key and rate-limiting enzyme for estrogen synthesis. Such interplay may have a considerable impact on the development of endometriosis.
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