Estrogen receptor-β, Estrogen receptor-α, and progesterone resistance in endometriosis

Serdar E. Bulun, You Hong Cheng, Mary Ellen Pavone, Qing Xue, Erkut Attar, Elena Trukhacheva, Hideki Tokunaga, Hiroki Utsunomiya, Ping Yin, Xia Luo, Zhihong Lin, Gonca Imir, Stephen Thung, Emily J. Su, J. Julie Kim

Research output: Contribution to journalReview article

135 Citations (Scopus)

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) promoter resulting in pathologic overexpression of ER 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-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.

Original languageEnglish (US)
Pages (from-to)36-43
Number of pages8
JournalSeminars in reproductive medicine
Volume28
Issue number1
DOIs
StatePublished - Feb 15 2010

Fingerprint

Endometriosis
Estrogen Receptors
Progesterone Receptors
Stromal Cells
Paracrine Communication
Molecular Models
Progesterone Resistance
Progestins
Endometrium
Epigenomics
Methylation
Progesterone
Protein Isoforms

Keywords

  • DNA methylation
  • ER-α
  • ER-β
  • Epigenetic
  • Gene regulation
  • PR
  • Progesterone resistance
  • Promoter
  • Transcription

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Reproductive Medicine
  • Endocrinology
  • Obstetrics and Gynecology
  • Physiology (medical)

Cite this

Bulun, Serdar E. ; Cheng, You Hong ; Pavone, Mary Ellen ; Xue, Qing ; Attar, Erkut ; Trukhacheva, Elena ; Tokunaga, Hideki ; Utsunomiya, Hiroki ; Yin, Ping ; Luo, Xia ; Lin, Zhihong ; Imir, Gonca ; Thung, Stephen ; Su, Emily J. ; Kim, J. Julie. / Estrogen receptor-β, Estrogen receptor-α, and progesterone resistance in endometriosis. In: Seminars in reproductive medicine. 2010 ; Vol. 28, No. 1. pp. 36-43.
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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) promoter resulting in pathologic overexpression of ER 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-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.",
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Bulun, SE, Cheng, YH, Pavone, ME, Xue, Q, Attar, E, Trukhacheva, E, Tokunaga, H, Utsunomiya, H, Yin, P, Luo, X, Lin, Z, Imir, G, Thung, S, Su, EJ & Kim, JJ 2010, 'Estrogen receptor-β, Estrogen receptor-α, and progesterone resistance in endometriosis', Seminars in reproductive medicine, vol. 28, no. 1, pp. 36-43. https://doi.org/10.1055/s-0029-1242991

Estrogen receptor-β, Estrogen receptor-α, and progesterone resistance in endometriosis. / Bulun, Serdar E.; Cheng, You Hong; Pavone, Mary Ellen; Xue, Qing; Attar, Erkut; Trukhacheva, Elena; Tokunaga, Hideki; Utsunomiya, Hiroki; Yin, Ping; Luo, Xia; Lin, Zhihong; Imir, Gonca; Thung, Stephen; Su, Emily J.; Kim, J. Julie.

In: Seminars in reproductive medicine, Vol. 28, No. 1, 15.02.2010, p. 36-43.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Estrogen receptor-β, Estrogen receptor-α, and progesterone resistance in endometriosis

AU - Bulun, Serdar E.

AU - Cheng, You Hong

AU - Pavone, Mary Ellen

AU - Xue, Qing

AU - Attar, Erkut

AU - Trukhacheva, Elena

AU - Tokunaga, Hideki

AU - Utsunomiya, Hiroki

AU - Yin, Ping

AU - Luo, Xia

AU - Lin, Zhihong

AU - Imir, Gonca

AU - Thung, Stephen

AU - Su, Emily J.

AU - Kim, J. Julie

PY - 2010/2/15

Y1 - 2010/2/15

N2 - 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) promoter resulting in pathologic overexpression of ER 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-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.

AB - 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) promoter resulting in pathologic overexpression of ER 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-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.

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KW - Promoter

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U2 - 10.1055/s-0029-1242991

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