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.

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.

• Authors: You-Hong Cheng, Ayse Imir, Veysel Fenkci, Mehmet Bertan Yilmaz, Serdar E Bulun
• Journal: American journal of obstetrics and gynecology (Am J Obstet Gynecol) Vol. 196 Issue 4 Pg. 391.e1-7; discussion 391.e7-8 (Apr 2007) ISSN: 1097-6868 [Electronic] United States
• PMID: 17403431 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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