| First Author | Han SJ | Year | 2019 |
| Journal | Endocrinology | Volume | 160 |
| Issue | 11 | Pages | 2495-2516 |
| PubMed ID | 31504401 | Mgi Jnum | J:287820 |
| Mgi Id | MGI:6363891 | Doi | 10.1210/en.2019-00442 |
| Citation | Han SJ, et al. (2019) Genomic Function of Estrogen Receptor beta in Endometriosis. Endocrinology 160(11):2495-2516 |
| abstractText | Estrogen receptor (ER) beta plays a critical role in endometriosis progression because cytoplasmic ERbeta stimulates proinflammatory signaling in ectopic lesions and prevents apoptosis to promote their survival. However, the role of "nuclear ERbeta" in endometriosis progression is not known. This critical knowledge gap obscures our understanding of the full molecular etiology of ERbeta-mediated endometriosis progression. To fill this void, we generated an ERbeta-regulated transcriptome and ERbeta cistrome in ectopic lesions and the eutopic endometrium of mice with endometriosis by using a new endometrium-specific FLAG-tagged human ERbeta overexpression mouse model. The integration of these omics data sets revealed that ERbeta stimulated the proliferation activities of ectopic lesions and the eutopic endometrium by directly upregulating MYC and E2 transcription factor target genes and genes associated with the G2/M transition. Additionally, ERbeta stimulated gene expression associated with TNFalpha/nuclear factor kappaB (NF-kappaB) signaling, epithelial-mesenchymal transition, reactive oxygen species signaling, IL-6/Janus kinase (JAK)/signal transducer and activator of transcription (STAT)3 signaling, and hypoxia signaling and suppressed IFNalpha signaling in ectopic lesions to enhance endometriosis progression. ERbeta also stimulated gene expression associated with the unfolded protein response and IL-6/JAK/STAT3 inhibitory signaling and suppressed TNFalpha/NF-kappaB signaling in the eutopic endometrium to cause endometriosis-associated endometrial dysfunction. Therefore, nuclear ERbeta-regulated gene networks provide critical clues to understand the molecular etiology and complexity of endometriosis and endometriosis-associated endometrial dysfunction. |
