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Inactivation of glucocorticoids by 11β-hydroxysteroid dehydrogenase(11βHSD) enzymes increases during the meiotic maturation of porcine oocytes

R Webb, Obstetrics & Gynaecology, St George's, University of London, London, United Kingdom
N Sunak, Biochemistry & Molecular Biology, UCL, London, United Kingdom
L Wren, Obstetrics & Gynaecology, St George's, University of London, London, United Kingdom
A Michael, Obstetrics & Gynaecology, St George's, University of London, London, United Kingdom

Correspondence: Rachel Webb, Email: rwebb{at}sgul.ac.uk

Abstract

Recent reports have shown that glucocorticoids can modulate oocyte maturation in both teleost fish and mammals. Within potential target cells, the actions of physiological glucocorticoids are modulated by 11β-hydroxysteroid dehydrogenase (11BHSD) isoenzymes which catalyse the inter-conversion of cortisol and cortisone. Hence the objective of this study was to establish whether 11βHSD enzymes mediate cortisol-cortisone metabolism in porcine oocytes and, if so, whether the rate of glucocorticoid metabolism changes during oocyte maturation. Enzyme activities were measured in cumulus-oocyte complexes (COCs) and denuded oocytes (DOs) using radiometric conversion assays. While COCs and DOs oxidised cortisol to inert cortisone, there was no detectable regeneration of cortisol from cortisone. The rate of cortisol oxidation was higher in expanded COCs than in compact COCs containing germinal vesicle (GV) stage oocytes (111±6 vs 2041±115 fmol cortisone/oocyte.24h; P<0.001). Likewise, 11βHSD activities were 17±1 fold higher in DOs from expanded COCs than in those from compact COCs (P<0.001). When GV stage oocytes were subject to a 48 hour in vitro maturation protocol, the enzyme activities were significantly increased from 146±18 to 1857±276 fmol cortisone/oocyte.24h in GV versus MII, respectively (P<0.001). Cortisol metabolism was inhibited by established pharmacological inhibitors of 11βHSD (glycyrrhetinic acid and carbenoxolone), and by porcine follicular and ovarian cyst fluid. We conclude that an 11βHSD enzyme (or enzymes) functions within porcine oocytes to oxidise cortisol, and that this enzymatic inactivation of cortisol increases during oocyte maturation.