Farnesoid X Receptor Agonist GW4064 Inhibits Aromatase and ERβ Expression in Human Endometriotic Stromal Cells

Wu PL, Pei-Li Wu, Peili Wu, Cheng Zeng, Zhou YF, Ying-Fang Zhou, Yingfang Zhou, Ling Yin, Yin L, Yu XL, Xiaolan Yu, Xiao-Lan Yu, Qing Xue, Xue Q
Reproductive sciences (Thousand Oaks, Calif.) · 2018 · vol. 26(8) , pp. 1111–1120 · doi:10.1177/1933719118808912 · PMID:30428773 · W2901898290
Lab / animal OA: closed CC0 ⤵ 4 in-corpus citations
View on OpenAlex View on PubMed View at publisher
⚙ AI-generated summary by gemini-2.5-flash-lite, 2026-06-07 ⓘ

The farnesoid X receptor agonist GW4064 was found to inhibit aromatase and ERβ expression in human endometriotic stromal cells.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

Abstract

Endometriosis is an estrogen-dependent disease. Farnesoid X receptor (FXR) activation has been shown to inhibit estrogen signaling in breast cancer and testicular tumors. However, the role of FXR in endometriosis is still poorly understood. Here, we aimed to investigate whether FXR activation by its synthetic agonist GW4064 has a therapeutic effect on endometriosis and the underlying molecular mechanisms. We found that the expression of FXR (encoded by the NR1H4 gene) in endometriotic tissues and stromal cells (ESCs) was higher than that in eutopic endometrial tissues and stromal cells. The GW4064 treatment led to a dose-dependent decrease in aromatase and estrogen receptor β (ERβ) expression and induced ERK1/2, p38, AMPK, and Stat3 activation in ESCs. In contrast, ERK1/2 inhibitor reversed the GW4064-induced reduction in aromatase expression. In addition, treatment with p38, AMPK, and Stat3 inhibitors or small interfering RNAs could also reverse the GW4064-induced reduction of ERβ expression in ESCs. The GW4064 treatment markedly increased Stat3 phosphorylation, enhancing the binding of Stat3 to the ESR2 promoter, which resulted in the downregulation of ERβ. Coimmunoprecipitation assay and chromatin immunoprecipitation analysis revealed that FXR was able to compete with cyclic AMP response element-binding (CREB) protein for binding to a common sequence on the aromatase promoter region after GW4064 treatment in ESCs. Moreover, treatment of endometriosis xenografts with GW4064 suppressed aromatase and ERβ expression in nude mice. Our results suggest that FXR may represent a potential therapeutic target for future therapy.

My notes (saved in your browser only)

MeSH descriptors

Aromatase Endometrium Estrogen Receptor beta Isoxazoles Receptors, Cytoplasmic and Nuclear Stromal Cells Adenylate Kinase Adenylate Kinase Adenylate Kinase Animals Animals Aromatase Aromatase Cyclic AMP Response Element-Binding Protein Cyclic AMP Response Element-Binding Protein Cyclic AMP Response Element-Binding Protein Endometrium Endometrium Endometrium Estrogen Receptor beta

Funding

funders
[{'doi': '10.13039/501100001809', 'name': 'National Natural Science Foundation of China', 'awards': ['81671427']}]

Citation neighborhood (2-hop)

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. Outer rings show 2-hop neighbours — papers reached through the immediate citers/citees. [ collapse to 1-hop ]

References (65)

Cited by (4)

Source provenance

crossref
last seen: 2026-07-27T06:55:23.974842+00:00
europepmc
last seen: 2026-10-16T06:09:50.462052+00:00
openalex
last seen: 2026-06-10T17:14:06.276822+00:00
pubmed
last seen: 2026-10-08T21:23:25.915063+00:00
unpaywall
last seen: 2026-10-16T06:24:35.758740+00:00
License: CC0 · commercial use OK