title: Inactivation of glucocorticoids by 11beta-hydroxysteroid dehydrogenase enzymes increases during the meiotic maturation of porcine oocytes.
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 11beta-hydroxysteroid dehydrogenase (HSD11B) isoenzymes that catalyse the interconversion of cortisol and cortisone. Hence, the objective of this study was to establish whether HSD11B 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.24 h; P<0.001). Likewise, HSD11B 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 h in vitro maturation protocol, the enzyme activities were significantly increased from 146+/-18 to 1857+/-276 fmol cortisone/oocyte.24 h in GV versus MII stage oocytes respectively (P<0.001). Cortisol metabolism was inhibited by established pharmacological inhibitors of HSD11B (glycyrrhetinic acid and carbenoxolone), and by porcine follicular and ovarian cyst fluid. We conclude that an HSD11B enzyme (or enzymes) functions within porcine oocytes to oxidise cortisol, and that this enzymatic inactivation of cortisol increases during oocyte maturation.
authors.affiliation: Division of Clinical Developmental Sciences, Academic Section of Obstetrics and Gynaecology, Centre for Developmental and Endocrine Signalling, St George's University of London, Cranmer Terrace, London, UK.
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Webb
authors.forename: Neera
authors.initials: N
authors.lastname: Sunak
authors.forename: Lisa
authors.initials: L
authors.lastname: Wren
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Michael
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D000818:Animals; D002229:Carbenoxolone / Q000494:pharmacology; D002478:Cells, Cultured; D003348:Cortisone / Q000378:metabolism; D005260:Female; D015571:Follicular Fluid / Q000201:enzymology; D005938:Glucocorticoids / Q000378:metabolism*; D006034:Glycyrrhetinic Acid / Q000494:pharmacology; D006854:Hydrocortisone / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D008540:Meiosis / Q000187:drug effects / Q000502:physiology*; D009865:Oocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D013552:Swine
chemical_list: D005938:Glucocorticoids; D007527:Isoenzymes; D042842:11-beta-Hydroxysteroid Dehydrogenases; D002229:Carbenoxolone; D006034:Glycyrrhetinic Acid; D003348:Cortisone; D006854:Hydrocortisone