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

Georgia Papacleovoulou, Richard J. Edmondson, Hilary O. D. Critchley, Stephen G. Hillier, J. Ian Mason

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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 3beta-hydroxysteroid dehydrogenase (3beta-HSD) by inflammatory, anti-inflammatory and apoptotic factors. In hOSE cells, we show that anti-inflammatory effects of IL-1alpha and IL-4 on 3beta-HSD2 mRNA involve a p38 MAPK signalling pathway, whereas pro-inflammatory response of IL-1alpha to 3beta-HSD1 mRNA involves a NF-kappaB inflammatory pathway. In OSE-C2 cells, retinoic acid and transforming growth factor-beta1 massively induce 3beta-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.
Original languageEnglish
Pages (from-to)65-73
Number of pages9
JournalMolecular and Cellular Endocrinology
Volume301
Issue number1-2
DOIs
Publication statusPublished - 25 Mar 2009

Keywords / Materials (for Non-textual outputs)

  • Human ovarian surface epithelium
  • OSE-C2 cells
  • 3β-HSD
  • Progesterone
  • Inflammation
  • Ovulation
  • Epithelial ovarian cancer

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