title: Role of estrogen receptor-β in endometriosis.
abstract: Endometriosis is an estrogen-dependent disease. The biologically active estrogen, estradiol, aggravates the pathological processes (e.g., inflammation and growth) and the symptoms (e.g., pain) associated with endometriosis. Abundant quantities of estradiol are available for endometriotic tissue via several mechanisms including local aromatase expression. The question remains, then, what mediates estradiol action. Because estrogen receptor (ER)β levels in endometriosis are >100 times higher than those in endometrial tissue, this review focuses on this nuclear receptor. Deficient methylation of the ERβ promoter results in pathological overexpression of ERβ in endometriotic stromal cells. High levels of ERβ suppress ERα expression. A severely high ERβ-to-ERα ratio in endometriotic stromal cells is associated with suppressed progesterone receptor and increased cyclo-oxygenase-2 levels contributing to progesterone resistance and inflammation. ERβ-selective estradiol antagonists may serve as novel therapeutics of endometriosis in the future.
authors.affiliation: Division of Reproductive Biology Research, Department Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA. s-bulun@northwestern.edu
authors.forename: Serdar E
authors.initials: SE
authors.lastname: Bulun
authors.forename: Diana
authors.initials: D
authors.lastname: Monsavais
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Pavone
authors.forename: Matthew
authors.initials: M
authors.lastname: Dyson
authors.forename: Qing
authors.initials: Q
authors.lastname: Xue
authors.forename: Erkut
authors.initials: E
authors.lastname: Attar
authors.forename: Hideki
authors.initials: H
authors.lastname: Tokunaga
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Su
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004715:Endometriosis / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D004717:Endometrium / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D044127:Epigenesis, Genetic / Q000187:drug effects; D004965:Estrogen Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D058990:Molecular Targeted Therapy; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D054339:Steroidogenic Factor 1 / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism
chemical_list: C506487:ESR1 protein, human; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; C515057:NR5A1 protein, human; D011980:Receptors, Progesterone; D054339:Steroidogenic Factor 1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human