title: 3beta-Hydroxysteroid dehydrogenases and pre-receptor steroid metabolism in the human ovarian surface epithelium.
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.
authors.affiliation: Reproductive and Developmental Sciences, Centre for Reproductive Biology, University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
authors.forename: Georgia
authors.initials: G
authors.lastname: Papacleovoulou
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Edmondson
authors.forename: Hilary O D
authors.initials: HO
authors.lastname: Critchley
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Hillier
authors.forename: J Ian
authors.initials: JI
authors.lastname: Mason
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D002460:Cell Line; D004848:Epithelium / Q000187:drug effects / Q000201:enzymology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000201:enzymology; D053582:Interleukin-1alpha / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D010053:Ovary / Q000187:drug effects / Q000201:enzymology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D053582:Interleukin-1alpha; D016328:NF-kappa B; D012333:RNA, Messenger; D011987:Receptors, Steroid; D053773:Transforming Growth Factor beta1; D015847:Interleukin-4; D014212:Tretinoin; D015096:3-Hydroxysteroid Dehydrogenases; D048051:p38 Mitogen-Activated Protein Kinases