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.

Stimuli from Conspecifics Influence Brain Mast Cell Population in Male Rats

“…Rat mast cells located in the bladder, upper airways, and dura mater and in the peritoneum are positive for estrogen receptor α (Pang, Marchand, Sant, Kream, and Theoharides, 1995;Vliagoftis, Dimitriadou, Boucher, Rozniecki, Correia, Raam, and Theoharides, 1992). We have now documented that rat thalamic mast cells express estrogen receptor α (Asarian, Silverman, and Silver, unpublished).…”

Microvascular effects of corticotropin-releasing hormone in human skin vary in relation to estrogen concentration during the menstrual cycle

“…There have been no specific reports of estrogen receptor localization in skin mast cells but this receptor has been localized in human mast cells of the bladder (Pang et al 1995), lung (Zhao et al 2001) and arterioles (Nicovani & Rudolph 2002). Furthermore in rat peritoneal mast cells, 17 -estradiol activated mast cell histamine and serotonin secretion (Vliagoftis et al 1992), suggesting mast cell degranulation can be directly regulated by this steroid. Based on this information we initiated the present study to examine the association between changes in estrogen concentration during the menstrual cycle and vascular responses to CRH, acetylcholine and heat.…”

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

“…(Harnish et al, 2004;Jiang et al, 2002;Nicovani and Rudolph, 2002;Zhao et al, 2001). Super-physiological concentrations of estradiol (E 2 , 1-10 μM) has been shown to induce (Spanos et al, 1996;Vliagoftis et al, 1992) or inhibit (Harnish et al, 2004) mast cell degranulation. Further, preincubating basophils or mast cells with physiological concentrations of E 2 has been shown to increase the subsequent histamine release induced by cross-linking surface-bound IgE with antibodies (Cocchiara et al, 1990;Cocchiara et al, 1992).…”