Steroid signalling in the ovarian surface epithelium.

Human ovarian surface epithelium (HOSE) undergoes serial injury-repair with each ovulation, which is probably why most ovarian epithelial cancers arise there. Considering the proposed inflammatory aetiology of ovarian cancer, anti-inflammatory steroid signalling might be vital for HOSE regulation. HOSE cells express hydroxysteroid dehydrogenase (HSD) enzymes that undertake prereceptor metabolism of bioinert steroidogenic precursors formed elsewhere in the body. Ovulation-associated cytokines activate anti-inflammatory cortisol from precursor cortisone in HOSE cells owing to up-regulation of the gene encoding 11betaHSD type 1 (HSD11B1) in vitro. Cortisol further enhances its own formation and action through augmentation of cytokine-induced HSD11B1 and glucocorticoid receptor gene expression. Understanding this feed-forward signalling process has implications for the improved diagnosis and treatment of inflammation-associated reproductive disease states such as ovarian cancer.