Cited by 243Endometriosis Research and TreatmentEstrogen and related hormone effectsEndometrial and Cervical Cancer Treatments

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

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Bulun, Serdar, Cheng, You-Hong, Pavone, Mary, Xue, Qing, Attar, Erkut, Trukhacheva, Elena, Tokunaga, Hideki, Utsunomiya, Hiroki, Yin, Ping, Luo, Xia, Lin, Zhihong, Imir, Gonca, Thung, Stephen, Su, Emily, Kim, J.·2010·Seminars in Reproductive Medicine

DOI 10.1055/s-0029-1242991PMC PMC3073375

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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)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.

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Authors: Bulun, S., Cheng, Y.-H., Pavone, M., Xue, Q., Attar, E., Trukhacheva, E., Tokunaga, H., Utsunomiya, H., Yin, P., Luo, X., Lin, Z., Imir, G., Thung, S., Su, E., & Kim, J.
Affiliations: Northwestern University (US)
Peking University (CN)
Istanbul University-Cerrahpaşa (TR)
Tohoku University (JP)
Yale University (US)
ORCID: Bulun, Serdar
Pavone, Mary
Xue, Qing
Attar, Erkut
Tokunaga, Hideki
Utsunomiya, Hiroki
Yin, Ping
Luo, Xia
Lin, Zhihong
Su, Emily
Kim, J.
Venue: Seminars in Reproductive Medicine
Publisher: Georg Thieme Verlag KG
Published: 2010-01
Volume: 28
Issue: 01
Pages: 036-043
ISSN: 1526-4564 (ISSN-L)
1526-8004
DOI: 10.1055/s-0029-1242991
PMC: PMC3073375
OpenAlex: W2091204496
Cited by: 243
References: 46
Citations by year: 2026: 17 · 2025: 10 · 2024: 17 · 2023: 10 · 2022: 11 · 2021: 20 · 2020: 19 · 2019: 11 · 2018: 16 · 2017: 8 · 2016: 12 · 2015: 21 · 2014: 20 · 2013: 17 · 2012: 14
FWCI: 19.43
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Seminars in Reproductive Medicine (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD040093, HD 040093, R01HD044715)
Topics: Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
Health Sciences › Medicine › Obstetrics and Gynecology › Endometrial and Cervical Cancer Treatments
Keywords: endometriosis, progesterone resistance, progesterone receptor, estrogen receptor beta, estrogen receptor alpha, endometriotic stromal cells, promoter methylation, epigenetic regulation, paracrine signaling
MeSH terms: Endometriosis, Endometrium, Female, Humans, Progesterone, Receptors, Progesterone, Gene Expression Regulation, Neoplastic, Stromal Cells, CpG Islands, DNA Methylation, Epigenesis, Genetic, Estrogen Receptor alpha, Estrogen Receptor beta

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

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