Human Reproduction, Vol. 17, No. 9, 2300-2306,
September 2002
© 2002 European Society of Human Reproduction and Embryology
Regulation of 11ß-hydroxysteroid dehydrogenase type 1 gene expression in human ovarian surface epithelial cells by interleukin-1
1 Assisted Conception Programme, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA and 2 Department of Reproductive and Developmental Sciences, University of Edinburgh Centre for Reproductive Biology, 49 Little France Crescent, Edinburgh EH16 4SB, UK
BACKGROUND: Local modulation of 11ß-hydroxysteroid dehydrogenase (11ßHSD) activity, to promote increased availability of anti-inflammatory glucocorticoids, is proposed as a compensatory response to inflammatory stimuli. Human 11ßHSD type 1 (11ßHSD1) is principally an 11-oxoreductase that reversibly reduces cortisone to cortisol. METHODS: Since ovulation is an acute inflammatory process, we examined the influence of pro-inflammatory cytokines on expression of 11ßHSD1 mRNA and metabolism of cortisone to cortisol by human ovarian surface epithelium (HOSE) in vitro. RESULTS: Northern analysis showed an 
1.5 kb-sized 11ßHSD1 mRNA transcript in total RNA that was up-regulated 3-fold by interleukin (IL)-1
(0.5 ng/ml) at 24 h. By real-time RT–PCR, induction of 11ßHSD1 mRNA by IL-1 was measurable at 6 h and maximal at 12 h. Primary HOSE cell cultures also showed low-level 11-oxoreductase activity that was stimulated time- and dose-dependently by IL-1 and IL-1ß. The 11ßHSD1 mRNA and 11-oxoreductase responses to 0.5 ng/IL were both suppressed by IL-1 receptor antagonist (25 ng/ml). CONCLUSIONS: Cultured HOSE cells express IL-1-responsive 11ßHSD1 and 11-oxoreductase activity mRNA in vitro. An 11ßHSD1-catalysed increase in anti-inflammatory glucocorticoid activity caused by pro-inflammatory cytokines could contribute to the local resolution of inflammation during ovulation.
Key words: cytokines/inflammation/ovarian surface epithelium/ovulation
3 To whom correspondence should be addressed. E-mail: s.hillier{at}ed.ac.uk
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