期刊
SEMINARS IN REPRODUCTIVE MEDICINE
卷 28, 期 1, 页码 36-43出版社
THIEME MEDICAL PUBL INC
DOI: 10.1055/s-0029-1242991
关键词
ER-beta; ER-alpha; PR; progesterone resistance; DNA methylation; epigenetic; promoter; gene regulation; transcription
资金
- NICHD [HD040093]
- Friends of Prentice
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENT [U54HD040093, R01HD044715] Funding Source: NIH RePORTER
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.
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