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

15 Citations (Scopus)

Abstract

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

  • 3-Hydroxysteroid Dehydrogenases
  • Adult
  • Cell Line
  • Epithelium
  • Female
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Inflammation
  • Interleukin-1alpha
  • Interleukin-4
  • MAP Kinase Signaling System
  • NF-kappa B
  • Ovary
  • RNA, Messenger
  • Receptors, Steroid
  • Transforming Growth Factor beta1
  • Tretinoin
  • p38 Mitogen-Activated Protein Kinases

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