Antiinflammatory steroid action in human ovarian surface epithelial cells.
The human ovarian surface epithelium (OSE) is subject to serial injury and repair during ovulation, which is a natural inflammatory event. We asked whether there is a compensatory antiinflammatory component to this process, involving steroid hormones produced locally at the time of ovulation. Quantitative RT-PCR analysis of total RNA from cultured human OSE cell monolayers showed that exposure to proinflammatory IL1alpha (500 pg/ml) increased mRNA levels of cyclooxygenase-2 (COX-2) (P < 0.01) at 48 h. The COX-2 mRNA response to IL1alpha was associated with an approximate 18-fold (P < 0.01) increase in mRNA levels of 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1), encoding the steroid dehydrogenase that reversibly reduces cortisone to antiinflammatory cortisol. Addition of cortisol to OSE cell culture medium dose-dependently suppressed the COX-2 mRNA response to IL1alpha (P < 0.01) but reciprocally enhanced the 11betaHSD1 mRNA response (P < 0.05), with both effects strongest at 1 microm cortisol. Presence of glucocorticoid receptor-alpha mRNA and protein was established in OSE cell monolayers and treatment with IL1alpha shown to significantly up-regulate the glucocorticoid receptor-alpha mRNA level (P < 0.05). Glucocorticoid receptor antagonist (RU486, 10 microm) fully reversed the inhibitory effect of 1 microm cortisol on IL1alpha-stimulated COX-2 mRNA expression. Progesterone also suppressed IL1alpha-induced COX-2 mRNA expression but had no significant effect on IL1alpha-stimulated 11betaHSD1 expression. These data provide direct evidence for antiinflammatory actions of cortisol and progesterone in human OSE cells.
Rae
Michael T
MT
Centre for Reproductive Biology, University of Edinburgh, Chancellors Building, 49 Little France Crescent, Edinburgh EH16 4SB, United Kingdom. mrae1@staffmail.ed.ac.uk
Niven
Deborah
D
Critchley
Hilary O D
HO
Harlow
Christopher R
CR
Hillier
Stephen G
SG
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D051546:Cyclooxygenase 2; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics; D008565:Membrane Proteins; D008875:Middle Aged; D015735:Mifepristone / Q000494:pharmacology; D010053:Ovary / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011965:Receptors, Glucocorticoid / Q000235:genetics
D000893:Anti-Inflammatory Agents; D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; C411470:glucocorticoid receptor alpha; D015735:Mifepristone; D011374:Progesterone; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D006854:Hydrocortisone