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

You Hong Cheng, Ayse Imir, Veysel Fenkci, Mehmet Bertan Yilmaz, Serdar E. Bulun*

*Corresponding author for this work

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Objective: In 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 17β-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 Design: We determined the effects of conditioned media generated from primary human eutopic endometrial stromal cells vs endometriotic stromal cells on Ishikawa malignant endometrial epithelial cells. Results: Conditioned media from progestin-pretreated eutopic endometrial stromal cells but not edometriotic stromal cells significantly stimulated specific protein-1 protein levels, 17β-hydroxysteroid dehydrogenase type 2 messenger RNA levels and promoter activity, and binding activity of specific protein-1 to the 17β-hydroxysteroid dehydrogenase type 2 promoter region in Ishikawa cells. Conclusion: A stromal cell defect in endometriosis blocks formation of progesterone-dependent production of factors leading to 17β-hydroxysteroid dehydrogenase type 2 deficiency and defective conversion of estradiol to estrone in epithelium.

Original languageEnglish (US)
Pages (from-to)391.e1-391.e8
JournalAmerican journal of obstetrics and gynecology
Volume196
Issue number4
DOIs
StatePublished - Apr 2007

Keywords

  • 17β-hydroxysteroid dehydrogenase type 2
  • R5020
  • conditioned medium
  • endometriosis
  • endometrium
  • epithelium
  • estradiol
  • estrone
  • paracrine
  • progesterone receptor
  • specific protein-1
  • stroma

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this