Glucocorticoid receptor-mediated regulation of MMP9 gene expression in human ovarian surface epithelial cells.
OBJECTIVE
To obtain proof-of-concept that locally produced anti-inflammatory steroids suppress ovulation-associated extracellular matrix proteases in human ovarian surface epithelial (OSE) cells.


METHODS
Primary OSE cell cultures treated with interleukin-1alpha (IL-1alpha) (500 pg/mL) as proxy for inflammation, with/without anti-inflammatory steroid (cortisol or progesterone [P], 0.01-1.0 microM).


METHODS
Academic medical center.


METHODS
Sixteen premenopausal women (29-46 years) undergoing surgery for nonmalignant gynecological conditions.


METHODS
Semiquantitative extracellular matrix protease gene expression profiling with verification by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and gelatinase zymography.


RESULTS
Treatment with IL-1alpha stimulated messenger RNA (mRNA) expression of several ovulation-associated matrix metalloproteinase genes by OSE cell cultures, including gelatinase B (MMP9) but not gelatinase A (MMP2). The IL-1alpha-stimulated MMP9 mRNA production was suppressed by cortisol but not P. Cortisol but not P also dose-dependently suppressed IL-1alpha-stimulated MMP9 gelatinase activity and this effect was blocked by the glucocorticoid receptor antagonist RU486.


CONCLUSIONS
In human OSE cells, stimulation of MMP9 gene expression and proteolytic activity by IL-1alpha is suppressed by anti-inflammatory cortisol through a glucocorticoid receptor-mediated mechanism. Because IL-1alpha also generates cortisol formation in OSE by stimulating cortisone reductase activity, these results support a role for intracrine cortisol in minimizing proteolytic damage to the OSE at ovulation.
Rae
Michael T
MT
Centre for Reproductive Biology, The Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, United Kingdom.
Price
Deborah
D
Harlow
Christopher R
CR
Critchley
Hilary O D
HO
Hillier
Stephen G
SG
D000328:Adult; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000201:enzymology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D010053:Ovary / Q000166:cytology* / Q000201:enzymology*; D011965:Receptors, Glucocorticoid / Q000378:metabolism*
D011965:Receptors, Glucocorticoid; D020780:Matrix Metalloproteinase 9