title: Disturbed balance between phase I and II metabolizing enzymes in ovarian endometriosis: a source of excessive hydroxy-estrogens and ROS?
abstract: Oxidative metabolism of estrogens was studied in 31 ovarian endometriosis and 29 normal endometrium samples, by qPCR. Expression was monitored for genes encoding five estrogen hydroxylating, five hydroxy (OH)-estrogen conjugating, and three estrogen quinone detoxifying enzymes. CYP1B1, COMT, NQO1, and GSTP1 protein levels were determined using Western blotting and immunohistochemistry staining. Increased expression of CYP1A1, CYP3A7 and COMT, and higher levels of MB-COMT were seen in endometriosis, as compared to normal endometrium. Expression of CYP1B1, CYP3A5, SULT1A1 and NQO2 was unchanged, with comparable CYP1B1 protein levels. Expression of SULT1E1, SULT2B1, UGT2B7, NQO1, and GSTP1 was decreased. Three NQO1 isoforms were detected; NQO1c appears to be endometriosis-specific. Our data indicate a disturbed balance between phase I and II metabolizing enzymes in endometriosis, potentially leading to excessive OH-estrogen and altered ROS formation, and stimulation of proliferation of ectopic endometrium. This is the first report on disturbed expression of estrogen oxidative metabolism genes in ovarian endometriosis.
authors.affiliation: Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Neli
authors.initials: N
authors.lastname: Hevir
authors.forename: Martina
authors.initials: M
authors.lastname: Ribič-Pucelj
authors.forename: Tea
authors.initials: T
authors.lastname: Lanišnik Rižner
mesh_terms: D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1; D004715:Endometriosis / Q000201:enzymology* / Q000235:genetics*; D004967:Estrogens / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D051549:Glutathione S-Transferase pi / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism; D050216:Metabolic Detoxication, Phase I / Q000235:genetics*; D050217:Metabolic Detoxication, Phase II / Q000235:genetics*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism; D010053:Ovary / Q000201:enzymology* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D039181:Steroid 16-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics; D055815:Young Adult
chemical_list: D004967:Estrogens; D007527:Isoenzymes; D017382:Reactive Oxygen Species; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D039181:Steroid 16-alpha-Hydroxylase; C020120:estrogen 2-hydroxylase; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D002394:Catechol O-Methyltransferase; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi