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

Am J Obstet Gynecol. 2007 Apr;196(4):391.e1-7; discussion 391.e7-8. doi: 10.1016/j.ajog.2006.12.014.

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 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 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 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.

Conclusion: A 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 17-Hydroxysteroid Dehydrogenases / genetics
  • 17-Hydroxysteroid Dehydrogenases / metabolism*
  • Adult
  • Biopsy, Needle
  • Down-Regulation
  • Endometriosis / metabolism
  • Endometriosis / pathology*
  • Endometrium / cytology*
  • Endothelial Cells / enzymology
  • Endothelial Cells / pathology
  • Estradiol / metabolism*
  • Female
  • Fibroblasts / enzymology
  • Fibroblasts / pathology
  • Humans
  • Immunoblotting
  • Intercellular Signaling Peptides and Proteins / biosynthesis*
  • Intercellular Signaling Peptides and Proteins / genetics
  • Multivariate Analysis
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Probability
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sampling Studies
  • Sensitivity and Specificity
  • Sp1 Transcription Factor / genetics
  • Sp1 Transcription Factor / metabolism*
  • Stromal Cells / enzymology
  • Stromal Cells / pathology
  • Transfection
  • Tumor Cells, Cultured
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology

Substances

  • Intercellular Signaling Peptides and Proteins
  • Sp1 Transcription Factor
  • Estradiol
  • 17-Hydroxysteroid Dehydrogenases
  • 3 (or 17)-beta-hydroxysteroid dehydrogenase