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.
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.


METHODS
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.


CONCLUSIONS
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.
Cheng
You-Hong
YH
Division of Reproductive Biology Research, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611-3095, USA.
Imir
Ayse
A
Fenkci
Veysel
V
Yilmaz
Mehmet Bertan
MB
Bulun
Serdar E
SE
D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D001707:Biopsy, Needle; D015536:Down-Regulation; D004715:Endometriosis / Q000378:metabolism / Q000473:pathology*; D004717:Endometrium / Q000166:cytology*; D042783:Endothelial Cells / Q000201:enzymology / Q000473:pathology; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000201:enzymology / Q000473:pathology; D006801:Humans; D015151:Immunoblotting; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D015999:Multivariate Analysis; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology; D011336:Probability; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D017154:Stromal Cells / Q000201:enzymology / Q000473:pathology; D014162:Transfection; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology
D036341:Intercellular Signaling Peptides and Proteins; D016329:Sp1 Transcription Factor; D004958:Estradiol; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase