TY - JOUR
T1 - 3β-Hydroxysteroid dehydrogenases and pre-receptor steroid metabolism in the human ovarian surface epithelium
AU - Papacleovoulou, Georgia
AU - Edmondson, Richard J.
AU - Critchley, Hilary O D
AU - Hillier, Stephen G.
AU - Mason, J. Ian
N1 - G0500047, Medical Research Council, United KingdomG0500047, Medical Research Council, United KingdomG0500047(73331), Medical Research Council, United Kingdom
PY - 2009/3/25
Y1 - 2009/3/25
N2 - 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. © 2008 Elsevier Ireland Ltd. All rights reserved.
AB - 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. © 2008 Elsevier Ireland Ltd. All rights reserved.
KW - 3β-HSD
KW - Epithelial ovarian cancer
KW - Human ovarian surface epithelium
KW - Inflammation
KW - OSE-C2 cells
KW - Ovulation
KW - Progesterone
U2 - 10.1016/j.mce.2008.08.010
DO - 10.1016/j.mce.2008.08.010
M3 - Article
C2 - 18778748
SN - 0303-7207
VL - 301
SP - 65
EP - 73
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
IS - 1-2
ER -