title: Estrogen receptor-beta, estrogen receptor-alpha, and progesterone resistance in endometriosis.
abstract: Loss of progesterone signaling in the endometrium may be a causal factor in the development of endometriosis, and progesterone resistance is commonly observed in women with this disease. In endometriotic stromal cells, the levels of progesterone receptor (PR), particularly the PR-B isoform, are significantly decreased, leading to a loss of paracrine signaling. PR deficiency likely underlies the development of progesterone resistance in women with endometriosis who no longer respond to progestin therapy. Here we review the complex epigenetic and transcriptional mechanisms leading to PR deficiency. The initial event may involve deficient methylation of the estrogen receptor (ER)beta promoter resulting in pathologic overexpression of ERbeta in endometriotic stromal cells. We speculate that alterations in the relative levels of ERbeta and ERalpha in endometrial tissue dictate E2-regulated PR expression, such that a decreased ERalpha-tauomicron-ERbeta ratio may result in suppression of PR. In this review, we propose a molecular model that may be responsible for changes in ERbeta and ERalpha leading to PR loss and progesterone resistance in endometriosis.
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: You-Hong
authors.initials: YH
authors.lastname: Cheng
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Pavone
authors.forename: Qing
authors.initials: Q
authors.lastname: Xue
authors.forename: Erkut
authors.initials: E
authors.lastname: Attar
authors.forename: Elena
authors.initials: E
authors.lastname: Trukhacheva
authors.forename: Hideki
authors.initials: H
authors.lastname: Tokunaga
authors.forename: Hiroki
authors.initials: H
authors.lastname: Utsunomiya
authors.forename: Ping
authors.initials: P
authors.lastname: Yin
authors.forename: Xia
authors.initials: X
authors.lastname: Luo
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Lin
authors.forename: Gonca
authors.initials: G
authors.lastname: Imir
authors.forename: Stephen
authors.initials: S
authors.lastname: Thung
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Su
authors.forename: J Julie
authors.initials: JJ
authors.lastname: Kim
mesh_terms: D018899:CpG Islands; D019175:DNA Methylation; D004715:Endometriosis / Q000235:genetics / Q000378:metabolism*; D004717:Endometrium / Q000378:metabolism; D044127:Epigenesis, Genetic; D047628:Estrogen Receptor alpha / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D011374:Progesterone / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000235:genetics; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D011980:Receptors, Progesterone; D011374:Progesterone