3beta-Hydroxysteroid dehydrogenases and pre-receptor steroid metabolism in the human ovarian surface epithelium.

Ovulation-associated inflammation with accompanied cytokines and reproductive hormones impact upon the human ovarian surface epithelium (hOSE) and probably have a role in the aetiology of ovarian cancer. Progesterone and progestin-related events, i.e. pregnancy and oral contraception, protect from the disease. We have investigated the pre-receptor metabolism of progesterone in primary hOSE cells and an immortalised hOSE cell line, OSE-C2, focusing on transcriptional regulation of 3β-hydroxysteroid dehydrogenase (3β-HSD) by inflammatory, anti-inflammatory and apoptotic factors. In hOSE cells, we show that anti-inflammatory effects of IL-1α and IL-4 on 3β-HSD2 mRNA involve a p38 MAPK signalling pathway, whereas pro-inflammatory response of IL-1α to 3β-HSD1 mRNA involves a NF-κB inflammatory pathway. In OSE-C2 cells, retinoic acid and transforming growth factor-β1 massively induce 3β-HSD1 mRNA levels. In conclusion, we elaborate several mechanisms for intracrine formation of progesterone in hOSE that could contribute in the development of novel strategies to prevent, diagnose and/or treat ovarian cancer.