Endocrine Abstracts (2004) 7 OC4

An anti-inflammatory role for progesterone at the human ovarian surface?

D Niven, MT Rae, HOD Critchley & SG Hillier


Centre for Reproductive Biology, University of Edinburgh, Edinburgh, Scotland.


Introduction:

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).

Methods:

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).

Results:

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.

Discussion:

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.

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