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Differential Effects of Lipid-lowering Drugs in Modulating Morphology of Cholesterol Particles
Published on: November 10, 2017
Lipoxin A4 is a novel estrogen receptor modulator.
Ronan Russell1, Ilaria Gori, Chiara Pellegrini
1Mucosal Immunity Laboratory, Department of Gynecology, Obstetrics and Medical Genetics, University Hospital Center and University of Lausanne, Ave. Pierre Decker 2, 1011 Lausanne, Switzerland.
Summary
Lipoxin A(4) (LXA(4)) exhibits dual estrogenic and antiestrogenic effects in the endometrium, acting via estrogen receptors. This lipid mediator plays a novel role in immunoendocrine crosstalk.
Area of Science:
- Reproductive biology
- Endocrinology
- Inflammation research
Background:
- Inflammation and tissue remodeling are linked in the endometrium.
- Lipoxins (LXs) are anti-inflammatory eicosanoids.
- The role of LXA(4) in endometrial function is largely unknown.
Purpose of the Study:
- To investigate the role of lipoxin A(4) (LXA(4)) in the human endometrium.
- To determine if LXA(4) interacts with estrogen signaling pathways.
Main Methods:
- Assessed 15-LOX-2 expression in endometrial tissue.
- Examined LXA(4)'s effects on estrogen-responsive elements (ERE) transcriptional activity, estrogen-regulated gene expression, alkaline phosphatase activity, and proliferation in human endometrial epithelial cells.
- Performed estrogen receptor (ER) binding assays.
- Evaluated LXA(4)'s in vivo effects on uterine wet weight and gene expression in a mouse model.
Main Results:
- 15-LOX-2, crucial for LX biosynthesis, is expressed in the endometrium.
- LXA(4) demonstrated estrogenic activity, upregulating ERE activity, estrogen-regulated genes, alkaline phosphatase, and proliferation.
- LXA(4) also exhibited antiestrogenic properties, inhibiting E2-induced activity.
- LXA(4) binds to ERα, mimicking 17β-estradiol (E2) and competing with E2 for ER binding (IC50 = 46 nM).
- In vivo, LXA(4) increased uterine wet weight and modulated E2-regulated gene expression.
Conclusions:
- LXA(4) possesses significant estrogenic and antiestrogenic activities in the endometrium, mediated exclusively through ERα.
- LXA(4) acts as a dual modulator of estrogen signaling, impacting endometrial epithelial cell function.
- These findings highlight a novel immunoendocrine crosstalk mechanism involving LXA(4) in the endometrium.
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