Disturbed balance between phase I and II metabolizing enzymes in ovarian endometriosis: A source of excessive hydroxy-estrogens and ROS?

Hevir N, Neli Hevir, Martina Ribič-Pucelj, Ribič-Pucelj M, Tea Lanišnik Rižner
Molecular and cellular endocrinology · 2012 · vol. 367(1-2) , pp. 74–84 · doi:10.1016/j.mce.2012.12.019 · PMID:23277161 · W2000224370
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This study investigated the balance of phase I and II metabolizing enzymes in ovarian endometriosis, hypothesizing a potential link to excessive hydroxy-estrogens and reactive oxygen species (ROS).

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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.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometriosis Estrogens Metabolic Detoxication, Phase I Metabolic Detoxication, Phase II Ovary Reactive Oxygen Species Adult Aryl Hydrocarbon Hydroxylases Aryl Hydrocarbon Hydroxylases Aryl Hydrocarbon Hydroxylases Blotting, Western Case-Control Studies Catechol O-Methyltransferase Catechol O-Methyltransferase Catechol O-Methyltransferase Cytochrome P-450 CYP1A1 Cytochrome P-450 CYP1A1 Cytochrome P-450 CYP1A1 Cytochrome P-450 CYP1B1

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