# The Genomic Function of Estrogen Receptor Beta in Endometriosis

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2022 · $377,462

## Abstract

As endometriosis is an estrogen-dependent inflammatory disease, estrogen/estrogen receptor (ER) signaling
has an essential role in the pathogenesis of endometriosis. We revealed that cytoplasmic ERβ interacts with the
apoptosis machinery and inflammasome complex in endometriotic tissues to prevent apoptosis and stimulate
cell proliferation activity, respectively. However, the function of nuclear ERβ in the pathogenesis of endometriosis
has not yet been elucidated. To fill this gap in the scientific knowledge, we have determined the endometriotic
tissue-specific ERβ-regulated transcriptome and ERβ-cistrome by using a novel endometrium-specific ERβ
overexpression mouse model. Our new omics data provided three unique aspects of nuclear ERβ function that
drive endometriosis progression. 1) The increases in anti-apoptosis signaling in the endometrium is one of the
critical drivers that promote the progression of endometriosis. Our omics data revealed that the ERβ/Nuclear
Factor of Activated T-cell 5 (NFAT5) complex directly downregulates the expression of N-Myc and STAT
Interactor (NMI), which stimulates interferon (IFN)α-induced cell death signaling. In Aim 1, we will investigate
the role of NMI in IFNα-induced cell death signaling in the normal endometrium and then identify whether the
ERβ/NFAT5 complex downregulates the expression of NMI in endometriotic lesions to enhance endometriosis.
Since epidermal growth factor receptor (EGFR) signaling is elevated in endometriotic tissue and involved in anti-
apoptosis, we will also investigate the role of EGFR in the ERβ/NFAT5-mediated suppression of NMI expression
in endometriotic tissues. 2) The epithelial-mesenchymal transition (EMT) is a critical step for endometriosis. Our
omics data showed that the ERβ/Early Growth Response Protein 1 (EGR1) axis directly increased the expression
of Fibrillin1 (FBN1), which is an activator of EMT, in ectopic lesions. In Aim 2, we will define the role of FBN1 in
endometriosis-associated EMT in ectopic lesions and then determine whether the ERβ/EGR1 axis upregulates
FBN1 gene expression in ectopic lesions to stimulate EMT in ectopic lesions. Since EGFR signaling also plays
an essential role in EMT, the role of EGFR in ERβ/EGR1 axis-mediated EMT will be investigated. 3) To establish
endometriosis, angiogenesis is activated in ectopic lesions. However, the molecular mechanism of estrogen-
induced angiogenesis in ectopic lesions has not been elucidated. Our data revealed that ERβ elevated the
expression of connective tissue growth factor (CTGF), which is the activator of hypoxia inducible factor 1a
(HIF1A)-mediated angiogenesis, in ectopic lesions. In Aim 3, we will define the role of CTGF in endometriosis-
associated angiogenesis and then determine whether the ERβ/HIF1A axis upregulates CTGF gene expression
in ectopic lesions to stimulate angiogenesis. Since EGFR signaling also plays an essential role in angiogenesis,
the role of EGFR in ERβ/HIF1A axis-mediated angiogenesi...

## Key facts

- **NIH application ID:** 10321675
- **Project number:** 5R01HD098059-03
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Sang Jun Han
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $377,462
- **Award type:** 5
- **Project period:** 2020-03-06 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10321675

## Citation

> US National Institutes of Health, RePORTER application 10321675, The Genomic Function of Estrogen Receptor Beta in Endometriosis (5R01HD098059-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10321675. Licensed CC0.

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