Estrogen is an important mediator of mast cell activation in ovarian endometriomas

Abstract

Endometriosis is an estrogen-dependent disease. Previous research has shown that abnormal enzymes associated with estrogen (E2) metabolism and an increased number of mast cells (MCs) in endometriomas are implicated in the pathogenesis of endometriosis. However, it remains unclear how MCs mediate the role of E2 in endometriosis. Accordingly, we investigated whether E2 was associated with the number of MCs, and the rate of degranulation, in local ovarian endometriomas, as well as the role of E2 on MCs during the pathogenesis of endometriosis. Using enzyme-linked immunosorbent assay and immunohistochemistry, we found that concentrations of E2, and the number and activity of MCs, were significantly higher in ovarian endometriomas than in controls, and that these parameters were correlated with the severity of endometriosis-associated dysmenorrhea. By measuring the release of hexosaminidase, we found that the rate of RBL2H3 cell degranulation increased after E2 treatment. Furthermore, activation of RBL2H3 cells by E2 was found to trigger the release of biologically active nerve growth factor, which promotes neurite outgrowth in PC12 cells and also sensitizes dorsal root ganglion cells via upregulation of and transient receptor potential cation channel (subfamily V member 1) expression levels. When treated with E2, endometriotic cells could promote RBL2H3 cell recruitment by upregulating expression levels of stem cell factor, transforming growth factor-β and monocyte chemoattractant protein-1; these observations were not evident with control endometrial cells. Thus, elevated E2 concentrations may be a key factor for degranulation and recruitment of MCs in ovarian endometriomas, which play a key role in endometriosis-associated dysmenorrhea.

The new application of mifepristone in the relief of adenomyosis-caused dysmenorrhea

“…Increasing evidence supports that activated and degranulating mast cells play an important role in the development of pain, hyperalgesia and dysmenorrhea [37,38]. Our previous study also demonstrate that the activity and degranulation of mast cells play an important role in endometriosis-related dysmenorrhea [14]. Moreover, it is reported that mast cells contribute to the development of inflammation in adenomyosis [10].…”

“…Furthermore, increasing evidence supports that the activated mast cell is regarded as a director of common inflammatory pathways contributing to chronic neuropathic pain and may play a role in pathogenesis of adenomyosis [11][12][13]. Our previous study also showed that the recruitment and degranulation of mast cells play an important role in endometriosis-related dysmenorrhea [14]. In addition, recent research found adenomyosis-induced pain resembles neuropathic pain [15].…”

“…As our previous study described, RBL2H3 cell degranulation was measured through the release of β-hexosaminidase [14]. RBL2H3 cells were seeded in 96-well plates (5 × 10 4 cells /well) with or without mifepristone treatment at the concentration of 50 μM for 48h.…”

Mast Cells as an Indicator and Prognostic Marker in Molecular Subtypes of Breast Cancer

“…Positive correlations between ER and MCs suggest that estrogen is a chemotactic molecule for MCs. We were especially interested in the correlation between MCit and ER + carcinoma cells, as some studies have proved that estrogen activates mast cells in ovarian endometriosis and that human uterine mast cells express ERβ (19,20). Others have shown that administration of estrogens leads to eosinophilic and MCs infiltrations (21).…”

Villainous role of estrogen in macrophage-nerve interaction in endometriosis

“…Endometriosis-associated inflammation is able to stimulate and sensitize peripheral nerves. Researchers found that activation of (DRG) mast cells by estrogen can trigger the release of NGF and also sensitize dorsal root ganglion cells [ 9 ]. This neuroimmune interaction mediated by estrogen is correlated with the severity of endometriosis-associated dysmenorrhea.…”