Antiinflammatory steroid action in human ovarian surface epithelial cells

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

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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-2 mRNA response 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 dose-dependently 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 microm 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 microm) fully reversed the inhibitory effect of 1 microm cortisol on IL1alpha-stimulated COX-2 mRNA expression. Progesterone also suppressed IL1alpha-induced COX-2 mRNA expression 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.
Original languageEnglish
Pages (from-to)4538-44
Number of pages7
JournalThe Journal of Clinical Endocrinology & Metabolism (JCEM)
Volume89
Issue number9
DOIs
Publication statusPublished - 2004

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