Platelets induce increased estrogen production through NF-κB and TGF-β1 signaling pathways in endometriotic stromal cells

Qiu-Ming Qi, Qiuming Qi, Xishi Liu, Qi Zhang, Sun‐Wei Guo
Scientific reports · 2020 · vol. 10(1) , pp. 1281 · doi:10.1038/s41598-020-57997-6 · PMID:31992765 · W3003511937
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⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

Activated platelets increase estrogen production in endometriotic stromal cells by upregulating estrogen synthesis genes via NF-κB and TGF-β1 signaling pathways.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-10 ⓘ

Qi and colleagues investigated whether activated human platelets can drive local estrogen overproduction in endometriotic stromal cells, using in vitro co-culture experiments measuring 17β-estradiol (E2) and the expression of key steroidogenic enzymes (StAR, HSD3B2, aromatase, and HSD17B1), along with upstream regulators. They found that activated platelets (but not thrombin alone) increased E2 production about 4.5-fold and increased both mRNA and protein levels of the four estrogen-synthesis genes, with upstream increases in HIF-1α, SF-1, and phosphorylated CREB; blocking either NF-κB or TGF-β1 signaling abolished the induction of these genes and the elevated estrogen production. Two animal experiments using platelet depletion/infusion and neutralization of NF-κB or TGF-β1 supported these cellular findings, and the paper explicitly frames lesions as wounds undergoing repeated injury and repair. This paper is centrally about endometriosis — it shows that activated platelets enhance estrogen biosynthesis in endometriotic stromal cells via NF-κB and TGF-β1 signaling.

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Abstract

Abstract Endometriosis is estrogen-dependent disorder. Two theories provide the explanations for the increased estrogen production. One is the feed-forward loop model linking inflammation and estrogen production. The more recent model evokes the tissue hypoxia resulting from endometrial debris detached and then regurgitated to the peritoneal cavity. Both models tacitly assume that everything occurs within the endometriotic stromal cells, seemingly without the need for exogenous factors. This study was undertaken to investigate as whether platelets may be responsible for local estrogen overproduction. We employed in vitro experimentation that evaluated the 17β-estradiol (E 2 ) levels in endometriotic stromal cells treated with activated platelets, and the genes and protein expression levels of StAR, HSD3B2, aromatase, and HSD17B1, as well as their upstream genes/proteins such as NF-κB, TGF-β1, HIF-1α, SF-1 and phosphorylated CREB. In addition, we conducted 2 animal experimentations using platelet depletion/infusion and also neutralization of NF-κB and TGF-β1, followed by immunohistochemistry analysis of involved in StAR, HSD3B2, aromatase, and HSD17B1, as well as SF-1 and p-CREB. We found that treatment of endometriotic stromal cells by activated platelets increase the E 2 production by 4.5 fold, and concomitant with increased gene and protein expression of StAR, HSD3B2, aromatase, and HSD17B1, the four genes/enzymes important to estrogen synthesis, along with their upstream genes HIF-1α, SF-1 and phosphorylated CREB. Moreover, platelets activate these genes through the activation of NF-κB and/or TGF-β1, and antagonism of either signaling pathway can abolish the induction of the 4 genes and thus increased estrogen production. The two animal experimentations confirmed these changes. Thus, platelets increase the E 2 production in endometriotic stromal cells through upregulation of StAR, HSD3B2, aromatase, and HSD17B1 via the activation of NF-κB and/or TGF-β1. These findings provide a yet another compelling piece of evidence that endometriotic lesions are indeed wounds undergoing repeated tissue injury and repair. They strongly indicate that non-hormonal therapeutics for endometriosis is theoretically viable, with anti-platelet therapy being one promising avenue.

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

Blood Platelets Endometriosis Endometrium Estrogens NF-kappa B Signal Transduction Transforming Growth Factor beta1 Blood Platelets Blood Platelets Endometriosis Endometriosis Endometrium Endometrium Estrogens Female Humans NF-kappa B Stromal Cells Stromal Cells Stromal Cells

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