Estrogen Receptor-β, Estrogen Receptor-α, and Progesterone Resistance in Endometriosis

被引：200

作者：

Bulun, Serdar E. ^{[1
]}

Cheng, You-Hong ^{[1
]}

Pavone, Mary Ellen ^{[1
]}

Xue, Qing ^{[2
]}

Attar, Erkut ^{[3
]}

Trukhacheva, Elena ^{[1
]}

Tokunaga, Hideki ^{[4
]}

Utsunomiya, Hiroki ^{[4
]}

Yin, Ping ^{[1
]}

Luo, Xia ^{[1
]}

Lin, Zhihong ^{[1
]}

Imir, Gonca ^{[5
]}

Thung, Stephen ^{[6
]}

Su, Emily J. ^{[1
]}

Kim, J. Julie ^{[1
]}

机构：

[1] Northwestern Univ, Feinberg Sch Med, Dept Obstet & Gynecol, Div Reprod Biol Res, Chicago, IL 60611 USA

[2] Peking Univ, Hosp 1, Dept Obstet & Gynecol, Beijing 100871, Peoples R China

[3] Istanbul Univ, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Capa Sch Med, Istanbul, Turkey

[4] Tohoku Univ, Sch Med, Dept Obstet & Gynecol, Sendai, Miyagi 980, Japan

[5] Cumhuriyet Univ, Sch Med, Dept Obstet & Gynecol, Sivas, Turkey

[6] Yale Univ, Sch Med, Dept Obstet & Gynecol, Div Maternal Fetal Med, New Haven, CT 06510 USA

来源：

SEMINARS IN REPRODUCTIVE MEDICINE | 2010年 / 28卷 / 01期

关键词：

ER-beta; ER-alpha; PR; progesterone resistance; DNA methylation; epigenetic; promoter; gene regulation; transcription; MESSENGER-RIBONUCLEIC-ACID; BREAST-CANCER CELLS; ELEMENT HALF-SITE; ACTIVATOR PROTEIN-1; BINDING-SITES; STROMAL CELLS; SP1; SITES; GENE; EXPRESSION; PROMOTER;

D O I：

10.1055/s-0029-1242991

中图分类号：

R71 [妇产科学];

学科分类号：

100211 ;

摘要：

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 ER beta in endometriotic stromal cells. We speculate that alterations in the relative levels of ER beta and ER alpha in endometrial tissue dictate E2-regulated PR expression, such that a decreased ER alpha-ER beta ratio may result in suppression of PR. In this review, we propose a molecular model that may be responsible for changes in ER beta and ER alpha leading to PR loss and progesterone resistance in endometriosis.

引用

页码：36 / 43

页数：8

共 49 条

[1] Progesterone receptor isoform A but not B is expressed in endometriosis [J].