Glucocorticoid receptor-mediated regulation of MMP9 gene expression in human ovarian surface epithelial cells

Rae, Michael T; Price, Deborah; Harlow, Christopher R; Critchley, Hilary O D; Hillier, Stephen G

Abstract

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.

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

Setting
Academic medical center.

Patient(s)
Sixteen premenopausal women (29–46 years) undergoing surgery for nonmalignant gynecological conditions.

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

Treatment with IL-1α 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-1α-stimulated MMP9 mRNA production was suppressed by cortisol but not P. Cortisol but not P also dose-dependently suppressed IL-1α-stimulated MMP9 gelatinase activity and this effect was blocked by the glucocorticoid receptor antagonist RU486.

Conclusion(s)
In human OSE cells, stimulation of MMP9 gene expression and proteolytic activity by IL-1α is suppressed by anti-inflammatory cortisol through a glucocorticoid receptor-mediated mechanism. Because IL-1α 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.

Citation

Rae, M. T., Price, D., Harlow, C. R., Critchley, H. O. D., & Hillier, S. G. (2009). Glucocorticoid receptor-mediated regulation of MMP9 gene expression in human ovarian surface epithelial cells. Fertility and Sterility, 92(2), 703-708. https://doi.org/10.1016/j.fertnstert.2008.06.040

• Journal Article Type: Article
• Acceptance Date: Jun 23, 2008
• Online Publication Date: Aug 22, 2008
• Publication Date: 2009-08
• Deposit Date: Aug 1, 2016
• Journal: Fertility and Sterility
• Print ISSN: 0015-0282
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 92
• Issue: 2
• Pages: 703-708
• DOI: https://doi.org/10.1016/j.fertnstert.2008.06.040
• Keywords: Ovarian surface epithelium, inflammation, ovulation, steroids, extracellular matrix, ovarian cancer
• Public URL: http://researchrepository.napier.ac.uk/Output/321384