Stromal cells of endometriosis fail to produce paracrine factors that induce epithelial 17β-hydroxysteroid dehydrogenase type 2 gene and its transcriptional regulator Sp1: a mechanism for defective estradiol metabolism

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Endometrial stromal cells from women with endometriosis lack the ability to produce paracrine factors that induce epithelial 17β-HSD2 gene expression and Sp1 binding, leading to impaired estradiol metabolism.

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Abstract

ObjectiveIn endometrium, stromal progesterone receptors mediate production of paracrine factors, which enhance binding of the transcription factor specific protein-1 to the promoter of the gene encoding the 17beta-hydroxysteroid dehydrogenase type 2 enzyme responsible for converting biologically active estradiol to estrone in epithelium. The objective of this study is to define the cellular defect responsible for the disruption of this stromal-epithelial interaction in endometriosis.Study designWe determined the effects of conditioned media generated from primary human eutopic endometrial stromal cells vs endometriotic stromal cells on Ishikawa malignant endometrial epithelial cells.ResultsConditioned media from progestin-pretreated eutopic endometrial stromal cells but not endometriotic stromal cells significantly stimulated specific protein-1 protein levels, 17beta-hydroxysteroid dehydrogenase type 2 messenger RNA levels and promoter activity, and binding activity of specific protein-1 to the 17beta-hydroxysteroid dehydrogenase type 2 promoter region in Ishikawa cells.ConclusionA stromal cell defect in endometriosis blocks formation of progesterone-dependent production of factors leading to 17beta-hydroxysteroid dehydrogenase type 2 deficiency and defective conversion of estradiol to estrone in epithelium.

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Condition tags

endometriosis

MeSH descriptors

17-Hydroxysteroid Dehydrogenases Endometriosis Endometrium Estradiol Intercellular Signaling Peptides and Proteins Sp1 Transcription Factor 17-Hydroxysteroid Dehydrogenases 17-Hydroxysteroid Dehydrogenases Adult Biopsy, Needle Down-Regulation Endometriosis Endometriosis Endometrium Endothelial Cells Endothelial Cells Endothelial Cells Estradiol Female Fibroblasts

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Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. Outer rings show 2-hop neighbours — papers reached through the immediate citers/citees. [ collapse to 1-hop ]

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