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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Sexual hormones regulate mast cell functionality and distribution in several tissues.
“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<i>ε</i>RI Expression in Rat Peritoneal Mast Cells (2015) · cites this paper as [11]
Estradiol has no effect on IgE-mediated mast cell secretion regardless of whether mast cells from female or male rats are used when high pharmacological concentrations of estradiol are used.
“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<i>ε</i>RI Expression in Rat Peritoneal Mast Cells (2015) · cites this paper as [11]
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Menzies, F. M., Henriquez, F. L., & Roberts, C. W. (2007) · Immunology Letters · doi:10.1016/j.imlet.2007.10.009 · Cited by 28 · see citing works
Targeting Mast Cells in Allergic Disease: Current Therapies and Drug Repurposing
Burchett, J. R., Dailey, J. M., Kee, S. A., Pryor, D. T., Kotha, A., Kankaria, R. A., Straus, D. B., & Ryan, J. J. (2022) · Cells · doi:10.3390/cells11193031 · Cited by 29 · see citing works
“Another study found that tamoxifen could reduce rat mast cell degranulation elicited by compound 48/80, substance P, or ionomycin [171].”
BackgroundTaiwo, O. B., Kovács, K. J., Sun, Y., & Larson, A. A. (2005) · Pain · doi:10.1016/j.pain.2004.12.002 · Cited by 28 · see citing works
“While estrogen alone does not influence mast cell activity, it increases the tendency for mast cells to degranulate in response to compounds such as substance P (Rozniecki et al., 1999; Vliagoftis et al., 1992) while testosterone exerts a stabilizing influence (Vliagoftis et al.”
BackgroundWeare-Regales, N., Carr, T. F., Holguín, F., Tibbitt, C. A., & Lockey, R. F. (2024) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2024.09.018 · Cited by 27 · see citing works
Song, W., Lee, S. M., Kim, M., Kim, S., Kim, K. W., Cho, S., Min, K., & Chang, Y. (2011) · Annals of Allergy Asthma & Immunology · doi:10.1016/j.anai.2011.07.012 · Cited by 26 · see citing works
GnRH, brain mast cells and behavior
Silverman, A., Asarian, L., Khalil, M., & Silver, R. (2002) · Progress in brain research · doi:10.1016/s0079-6123(02)41102-8 · Cited by 26 · see citing works
“, 1993), substance P or Compound 48/80 (a polyamine known to stimulate mast cell secretion) (Vliagoftis et al., 1992).”
BackgroundEstrogen Dermatitis: A Dendritic-Cell-Mediated Allergic Condition
Yotsumoto, S., Shimomai, K., Hashiguchi, T., et al. (2003) · Dermatology · doi:10.1159/000073088 · Cited by 25 · see citing works
Açar, D., Çayan, S., Aktaş, S., et al. (2006) · Neurourology and Urodynamics · doi:10.1002/nau.20247 · Cited by 24 · see citing works
Physiological mechanisms of unexplained (functional) gastrointestinal disorders
Burns, G. L., Hoedt, E. C., Walker, M. M., Talley, N. J., & Keely, S. (2021) · The Journal of Physiology · doi:10.1113/jp281620 · Cited by 23 · see citing works
“2019), the decrease in concentration of these hormones at menses may result in a reduction in epithelial integrity, and oestrogen has been shown to increase mast cell secretion in a substance P-, but not IgE-dependent manner (Vliagoftis et al. 1992).”
BackgroundBauza, D. E. R., & Silveyra, P. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17197270 · Cited by 22 · see citing works
Izzo, G., d'Istria, M., Serino, I., et al. (2003) · Journal of Experimental Biology · doi:10.1242/jeb.00786 · Cited by 22 · see citing works
“These effects are counteracted by tamoxifen, an antiestrogen (Vliagoftis et al., 1992).”
BackgroundInfluentialFood Allergy: An Increasing Problem for the Elderly
Möhrenschlager, M., & Ring, J. (2010) · Gerontology · doi:10.1159/000316576 · Cited by 22 · see citing works
A study of androgen and estrogen receptors α, β in skin tags
Omar, E. S., Rashid, L., & Ibrahim, M. M. (2010) · Indian Journal of Dermatology · doi:10.4103/0019-5154.60345 · Cited by 21 · see citing works
“[18] Considering the fact that mast cells are a major player in the development of skin tags, [15] and the effect of androgens on their concentration and behavior, androgens can have a role in the pathogenesis of skin tags.”
- 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 › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Physiology › 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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