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Semin Reprod Med 2010; 28(1): 036-043
DOI: 10.1055/s-0029-1242991
© Thieme Medical Publishers

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

Serdar E. Bulun1 , You-Hong Cheng1 , Mary Ellen Pavone1 , Qing Xue2 , Erkut Attar3 , Elena Trukhacheva1 , Hideki Tokunaga4 , Hiroki Utsunomiya4 , Ping Yin1 , Xia Luo1 , Zhihong Lin1 , Gonca Imir5 , Stephen Thung6 , Emily J. Su1 , J. Julie Kim1
  • 1Division of Reproductive Biology Research, Department Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
  • 2Department of Obstetrics and Gynecology, First Hospital of Peking University, Beijing, P.R. China
  • 3Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Istanbul University Capa School of Medicine, Istanbul, Turkey
  • 4Department of Obstetrics and Gynecology, Tohoku University School of Medicine, Sendai, Japan
  • 5Department of Obstetrics and Gynecology, Cumhuriyet University School of Medicine, Sivas, Turkey
  • 6Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut
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Publication History

Publication Date:
26 January 2010 (online)

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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)β promoter resulting in pathologic overexpression of ERβ in endometriotic stromal cells. We speculate that alterations in the relative levels of ERβ and ERα in endometrial tissue dictate E2-regulated PR expression, such that a decreased ERα-το-ERβ ratio may result in suppression of PR. In this review, we propose a molecular model that may be responsible for changes in ERβ and ERα leading to PR loss and progesterone resistance in endometriosis.

KEYWORDS

ER-β - ER-α - PR - progesterone resistance - DNA methylation - epigenetic - promoter - gene regulation - transcription

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Serdar E BulunM.D. 

George H. Gardner Professor of Clinical Gynecology, Division of Reproductive Biology Research, Department Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine

303 E. Superior St., 4-123 Chicago, IL 60611

Email: s-bulun@northwestern.edu