Reduced expression of progesterone receptor-B in the endometrium of women with endometriosis and in cocultures of endometrial cells exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
OBJECTIVE
To analyze endometrial progesterone receptor (PR) expression in women with endometriosis compared with disease-free women and to assess the impact of in vitro 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure on PR isotype expression.


METHODS
Controlled laboratory study.


METHODS
University medical center.


METHODS
Healthy volunteers and women with surgically diagnosed endometriosis.


METHODS
None.


METHODS
Analysis of in vivo PR-A and PR-B expression in endometrium from women with and without endometriosis. The impact of in vitro TCDD exposure on PR-B/PR-A ratio and cell-specific matrix metalloproteinase (MMP) expression was also determined.


RESULTS
The PR-B/PR-A ratio was lower in endometrial tissues from women with endometriosis compared with normal tissues. A similar ratio was induced in normal stromal cells cocultured with epithelial cells and exposed to TCDD. Disruption of stromal PR expression following TCDD exposure was associated with a failure of P-mediated down-regulation of both stromal-specific pro-MMP-3 and epithelial-specific pro-MMP-7.


CONCLUSIONS
Our data suggest that reduced progesterone (P) sensitivity in the endometrium of women with endometriosis may be related to an altered pattern of PR expression. The ability of TCDD to selectively down-regulate stromal PR-B expression and increase MMP expression in both stromal and epithelial cells suggests that exposure to this toxin may negatively impact P-mediated cell-cell communication in the human endometrium.
Igarashi
Toshio M
TM
Women's Reproductive Health Research Center, Department of Obstetrics and Gynecology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Bruner-Tran
Kaylon L
KL
Yeaman
Grant R
GR
Lessey
Bruce A
BA
Edwards
Dean P
DP
Eisenberg
Esther
E
Osteen
Kevin G
KG
D000328:Adult; D002478:Cells, Cultured; D018920:Coculture Techniques; D004715:Endometriosis / Q000235:genetics / Q000378:metabolism*; D004717:Endometrium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D020782:Matrix Metalloproteinases / Q000096:biosynthesis / Q000235:genetics; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011980:Receptors, Progesterone / Q000096:biosynthesis* / Q000235:genetics; D018709:Statistics, Nonparametric; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D000072317:Polychlorinated Dibenzodioxins; D011980:Receptors, Progesterone; C097314:progesterone receptor B; D020782:Matrix Metalloproteinases