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Estradiol Augments while Tamoxifen Inhibits Rat Mast Cell Secretion
Abstract
Mast cells have been studied extensively for their involvement in allergic reactions, where they secrete numerous powerful mediators in response to immunoglobulin E and specific antigens. However, they are also triggered by neuropeptides, they have been found in close contact with neurons, and they are activated in diseases such as angioedema, interstitial cystitis and irritable bowel disease, the prevalence of which is much higher in women. When tested on purified rat peritoneal mast cells, 17β-estradiol augmented secretion of histamine and serotonin, starting at 1 μM and in a dose-dependent manner, whether stimulated by the mast cell secretagogue compound 48/80 or the neuropeptide substance P. However, 17β-estradiol did not augment mast cell secretion stimulated by immunoglobulin E and specific antiserum indicating that immunologic stimulation is under different regulation. Testosterone inhibited secretion induced by compound 48/80. Tamoxifen, an estrogen receptor antagonist used in the treatment of breast cancer, inhibited serotonin and histamine release from purified rat peritoneal mast cells triggered by compound 48/80 or substance P. Tamoxifen also inhibited the increase in intracellular free Ca2+ originating from an influx of extracellular Ca2+ in response to compound 48/80. Moreover, tamoxifen antagonized the synergistic effect of phorbol myristate and the cation ionophore A23187 on mast cell secretion, suggesting that tamoxifen’s inhibition may be due to regulation of protein kinase C activity. Tamoxifen may, therefore, have a beneficial effect in other neuroimmunoendocrine disorders both through estrogen receptor blockade and inhibition of mast cell secretion.
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“A number of in vivo and in vitro studies suggest that sexual hormones regulate MCs functionality and distribution in several tissues [10–14].”
From Gender-Related Effects of Sex Steroids on Histamine Release and Fc ε RI Expression in Rat Peritoneal Mast Cells (2015) · cites this paper as [11]
In the citing paper
“In contrast, it was reported that estradiol has no effect on IgE-mediated MC secretion, regardless of whether MCs from female or male rats were used; however, these results were derived using high concentrations (pharmacological) of estradiol [11].”
From Gender-Related Effects of Sex Steroids on Histamine Release and Fc ε RI Expression in Rat Peritoneal Mast Cells (2015) · cites this paper as [11]
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Metadata
- Authors
- Vliagoftis, H., Dimitriadou, V., Boucher, W., Rozniecki, J. J., Correia, I., Raam, S., & Theoharides, T. C.
- Affiliations
- Tufts University (US)
- Venue
- International Archives of Allergy and Immunology
- Publisher
- S. Karger AG
- Published
- 2009-09-02
- Volume
- 98
- Issue
- 4
- Pages
- 398-409
- ISSN
- 1018-2438 (ISSN-L)
- 1423-0097
- OpenAlex
- W1963785160
- Cited by
- 158
- References
- 0
- Citations by year
- 2026: 3 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 3 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 5 · 2015: 8 · 2014: 3 · 2013: 2 · 2012: 5
- FWCI
- 4.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Archives of Allergy and Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01dk042409-03)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK42409)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Asthma and respiratory diseases
- Keywords
- mast cell secretion, estradiol, tamoxifen, estrogen receptor antagonism, histamine release, serotonin release, compound 48/80, substance P, intracellular calcium, protein kinase C, testosterone, peritoneal mast cells, angioedema, irritable bowel disease
- MeSH terms
- Animals, Calcium, Estradiol, Exocytosis, Histamine Release, Male, Mast Cells, Protein Kinase C, Receptors, Estrogen, Serotonin, Tamoxifen, Testosterone, Cell Degranulation, Rats, Sprague-Dawley, Rats, In Vitro Techniques
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