The ovarian surface epithelium (OSE) covers the surface of the ovary, and is subjected to rupture and repair during ovulation. Ovulation bears hallmarks of a wound / heal event, including inflammation. Though integral to ovulation, inflammation may cause cellular damage leading to ovarian tumours, of which >90% are OSE derived. Progesterone, produced in large amounts at ovulation, has anti-inflammatory properties. The aim of this study was to determine effects of progesterone on OSE gene expression induced by an inflammatory cytokine associated with ovulation, Interleukin 1alpha (IL1alpha).
Human OSE were collected from women undergoing surgery for benign gynaecological conditions, with informed consent and local ethical committee approval. Primary cultures were treated plus/minus500 picogrammes per millilitre IL1alpha, plus/minus a dose range of progesterone (1, 0.1 and 0.01micromolar), for 48 hours. Medium was analysed by zymography for metalloproteinases-2 and -9 (MMP-2 and -9), western blotting for tissue inhibitor of metalloproteinases-1(TIMP-1), and real-time PCR used to measure gene expression of 11beta hydroxysteroid dehydrogenase types 1 and 2 (11betaHSDt1, 11betaHSDt2) and Cyclooxygenase 2 (COX-2).
IL1alpha alone increased expression of COX-2 (P<0.01), 11betaHSD1 (P<0.01), MMP-9 activity (P<0.01), but not 11betaHSD2 mRNA. Progesterone alone had no effects in this system, but decreased IL1alpha-induced COX-2 expression, with no effect on any of the other parameters measured.
IL1alpha induced gene expression in OSE associated with inflammation (COX-2), tissue remodelling (MMP-9) and anti-inflammatory glucocorticoid generation (11betaHSDt1). Progesterone reversed IL1alpha-induced COX-2 expression, but had no effects on either MMP-9 or 11betaHSDt1. These results suggest that in OSE, progesterone may, around the time of ovulation, restrain deleterious, inflammation-induced responses associated with prostaglandin formation, without affecting genes required for OSE remodelling and subsequent formation of the corpus luteum.