Antiinflammatory steroid action in human ovarian surface epithelial cells

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 IL1α (500 pg/ml) increased mRNA levels of cyclooxygenase-2 (COX-2) (P < 0.01) at 48 h. The COX-2 mRNA response to IL1α was associated with an approximate 18-fold (P < 0.01) increase in mRNA levels of 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1), 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 IL1α (P < 0.01) but reciprocally enhanced the 11βHSD1 mRNA response (P < 0.05), with both effects strongest at 1 μM cortisol. Presence of glucocorticoid receptor-α mRNA and protein was established in OSE cell monolayers and treatment with IL1a shown to significantly up-regulate the glucocorticoid receptor-α mRNA level (P < 0.05). Glucocorticoid receptor antagonist (RU486,10 μM) fully reversed the inhibitory effect of 1 μM cortisol on IL1α-stimulated COX-2 mRNA expression. Progesterone also suppressed IL1α-induced COX-2 mRNA expression but had no significant effect on IL1α-stimulated 11βHSD1 expression. These data provide direct evidence for antiinflammatory actions of cortisol and progesterone in human OSE cells.