Antiinflammatory Steroid Action in Human Ovarian Surface Epithelial Cells

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

Abstract

The human ovarian surface epithelium (OSE) is subject to
serial injury and repair during ovulation, which is a natural inflammatory event. We asked whether there is a compensatory antiinflammatory component to this process, involving steroid hormones produced locally at the time of ovulation. Quantitative RT-PCR analysis of total RNA from cultured human OSE cell monolayers showed that exposure to proinflammatory IL1Alpha (500 pg/ml) increased mRNA levels of cyclooxygenase-2 (COX-2) (P < 0.01) at 48 h. The COX-2mRNAresponse to IL1Alpha was associated with an approximate 18-fold (P < 0.01) increase in mRNA levels of 11Beta-hydroxysteroid dehydrogenase type 1 (11BetaHSD1), encoding the steroid dehydrogenase that reversibly reduces cortisone to antiinflammatory cortisol. Addition of cortisol to OSE cell culture medium dosedependently
suppressed the COX-2 mRNA response to IL1Alpha (P < 0.01) but reciprocally enhanced the 11BetaHSD1 mRNA response
(P < 0.05), with both effects strongest at 1 muM cortisol.
Presence of glucocorticoid receptor-Alpha mRNA and protein was established in OSE cell monolayers and treatment with IL1Alpha shown to significantly up-regulate the glucocorticoid receptor- Alpha mRNA level (P < 0.05). Glucocorticoid receptor antagonist (RU486, 10 muM) fully reversed the inhibitory effect of 1 muM cortisol on IL1Alpha-stimulated COX-2 mRNA expression. Progesterone also suppressed IL1Alpha-induced COX-2mRNAexpression but had no significant effect on IL1Alpha-stimulated 11BetaHSD1 expression. These data provide direct evidence for antiinflammatory actions of cortisol and progesterone in human OSE cells.

Citation

Hillier, S. G., Rae, M. T., Niven, D., Critchley, H. O. D., & Harlow, C. R. (2004). Antiinflammatory Steroid Action in Human Ovarian Surface Epithelial Cells. Journal of Clinical Endocrinology and Metabolism, 89(9), 4538-4544. https://doi.org/10.1210/jc.2003-032225

• Journal Article Type: Article
• Publication Date: Sep 1, 2004
• Deposit Date: Jun 25, 2008
• Journal: The Journal of Clinical Endocrinology & Metabolism
• Print ISSN: 0021-972X
• Electronic ISSN: 1945-7197
• Publisher: Endocrine Society
• Peer Reviewed: Peer Reviewed
• Volume: 89
• Issue: 9
• Pages: 4538-4544
• DOI: https://doi.org/10.1210/jc.2003-032225
• Keywords: Humans; Ovaries; Epithelium; Anti-inflammatory; Steroids; Biochemistry
• Public URL: http://researchrepository.napier.ac.uk/id/eprint/1661
• Publisher URL: http://dx.doi.org/10.1210/jc.2003-032225