Estrogen Receptor β Modulates Apoptosis Complexes and the Inflammasome to Drive the Pathogenesis of Endometriosis

Sang Jun Han, Sung Yun Jung, San Pin Wu, Shannon M. Hawkins, Mi Jin Park, Satoru Kyo, Jun Qin, John P. Lydon, Sophia Y. Tsai, Ming Jer Tsai, Francesco J. Demayo, Bert W. O'Malley

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96 Scopus citations


Summary Alterations in estrogen-mediated cellular signaling play an essential role in the pathogenesis of endometriosis. In addition to higher estrogen receptor (ER) β levels, enhanced ERβ activity was detected in endometriotic tissues, and the inhibition of enhanced ERβ activity by an ERβ-selective antagonist suppressed mouse ectopic lesion growth. Notably, gain of ERβ function stimulated the progression of endometriosis. As a mechanism to evade endogenous immune surveillance for cell survival, ERβ interacts with cellular apoptotic machinery in the cytoplasm to inhibit TNF-α-induced apoptosis. ERβ also interacts with components of the cytoplasmic inflammasome to increase interleukin-1β and thus enhance its cellular adhesion and proliferation properties. Furthermore, this gain of ERβ function enhances epithelial-mesenchymal transition signaling, thereby increasing the invasion activity of endometriotic tissues for establishment of ectopic lesions. Collectively, we reveal how endometrial tissue generated by retrograde menstruation can escape immune surveillance and develop into sustained ectopic lesions via gain of ERβ function.

Original languageEnglish (US)
Pages (from-to)960-974
Number of pages15
Issue number4
StatePublished - Nov 5 2015


ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Han, S. J., Jung, S. Y., Wu, S. P., Hawkins, S. M., Park, M. J., Kyo, S., Qin, J., Lydon, J. P., Tsai, S. Y., Tsai, M. J., Demayo, F. J., & O'Malley, B. W. (2015). Estrogen Receptor β Modulates Apoptosis Complexes and the Inflammasome to Drive the Pathogenesis of Endometriosis. Cell, 163(4), 960-974.