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Mol Immunol. 2007 Mar;44(8):1977-85. Epub 2006 Nov 3.

Estradiol activates mast cells via a non-genomic estrogen receptor-alpha and calcium influx.

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Department of Pediatrics, Child Health Research Center, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-0366, USA.



Allergic airway diseases are more common in females than in males during early adulthood. A relationship between female hormones and asthma prevalence and severity has been suggested, but the cellular and molecular mechanisms are not understood.


To elucidate the mechanism(s) by which estrogens enhance the synthesis and release of mediators of acute hypersensitivity.


Two mast cell/basophil cell lines (RBL-2H3 and HMC-1) and primary cultures of bone marrow derived mast cells, all of which naturally express estrogen receptor-alpha, were examined. Cells were incubated with physiological concentrations of 17-beta-estradiol with and without IgE and allergens. Intracellular Ca(2+) concentrations and the release of beta-hexosaminidase and leukotriene C(4) were quantified.


Estradiol alone induced partial release of the preformed, granular protein beta-hexosaminidase from RBL-2H3, BMMC and HMC-1, but not from BMMC derived from estrogen receptor-alpha knock-out mice. The newly synthesized LTC(4) was also released from RBL-2H3. Estradiol also enhanced IgE-induced degranulation and potentiated LTC(4) production. Intracellular Ca(2+) concentration increased prior to and in parallel with mediator release. Estrogen receptor antagonists or Ca(2+) chelation inhibited these estrogenic effects.


Binding of physiological concentrations of estradiol to a membrane estrogen receptor-alpha initiates a rapid onset and progressive influx of extracellular Ca(2+), which supports the synthesis and release of allergic mediators. Estradiol also enhances IgE-dependent mast cell activation, resulting in a shift of the allergen dose response.

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