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.

• 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