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Gender-related effects of sex steroids on histamine release and FcεRI expression in rat peritoneal mast cells.

Muñoz-Cruz S, Mendoza-Rodríguez Y, Nava-Castro KE, Yepez-Mulia L, Morales-Montor J - J Immunol Res (2015)

Bottom Line: Our results demonstrated that effect of sex steroids on MCs histamine release is dose- and gender-dependent and can be direct, synergistic, or inhibitory depending on whether hormones are used alone or to pretreat MCs followed by substance P-stimulation or upon IgE-mediated stimulation.In contrast, sex steroids did not have effect on the MC expression of the IgE high affinity receptor, FcεRI, no matter female or male rats were used.In conclusion, MCs degranulation is modulated by sex hormones in a gender-selective fashion, with MC from females being more susceptible than MC from males to the effects of sex steroids.

View Article: PubMed Central - PubMed

Affiliation: Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, Instituto Mexicano del Seguro Social, 06720 México, DF, Mexico.

ABSTRACT
Mast cells (MCs) are versatile effector and regulatory cells in various physiologic, immunologic, and pathologic processes. In addition to the well-characterized IgE/FcεRI-mediated degranulation, a variety of biological substances can induce MCs activation and release of their granule content. Sex steroids, mainly estradiol and progesterone, have been demonstrated to elicit MCs activation. Most published studies have been conducted on MCs lines or freshly isolated peritoneal and bone marrow-derived MC without addressing gender impact on MC response. Our goal was to investigate if the effect of estradiol, progesterone, testosterone, and dihydrotestosterone (DHT) on MCs may differ depending on whether female or male rats are used as MCs donors. Our results demonstrated that effect of sex steroids on MCs histamine release is dose- and gender-dependent and can be direct, synergistic, or inhibitory depending on whether hormones are used alone or to pretreat MCs followed by substance P-stimulation or upon IgE-mediated stimulation. In contrast, sex steroids did not have effect on the MC expression of the IgE high affinity receptor, FcεRI, no matter female or male rats were used. In conclusion, MCs degranulation is modulated by sex hormones in a gender-selective fashion, with MC from females being more susceptible than MC from males to the effects of sex steroids.

No MeSH data available.


Related in: MedlinePlus

Effect of gender and sex steroid concentration on histamine release induced by substance P in mast cells. Rat PMCs were pretreated with E2, P4, T4, and DHT at 10 pM to 10 nM for 90 min at 37°C, followed by 30 min incubation with 10 μM of substance P. Values are means ± SEM of three independent experiments in triplicate. *P < 0.05, **P < 0.01, and ***P < 0.001 with and without hormone. Comparisons between genders were performed by one-way analysis of variance (ANOVA), followed by Bonferroni's multiple comparison test (GraphPad Prism). Hormone concentration and gender had significant effect and the interaction is statistically significant (P < 0.001).
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fig2: Effect of gender and sex steroid concentration on histamine release induced by substance P in mast cells. Rat PMCs were pretreated with E2, P4, T4, and DHT at 10 pM to 10 nM for 90 min at 37°C, followed by 30 min incubation with 10 μM of substance P. Values are means ± SEM of three independent experiments in triplicate. *P < 0.05, **P < 0.01, and ***P < 0.001 with and without hormone. Comparisons between genders were performed by one-way analysis of variance (ANOVA), followed by Bonferroni's multiple comparison test (GraphPad Prism). Hormone concentration and gender had significant effect and the interaction is statistically significant (P < 0.001).

Mentions: The neuropeptide substance P was used to analyze the effect of sex hormones on histamine released induced by a classic MC secretagogue. Pretreatment of PMCs from female rats with E2, P4, T4, and DHT at physiological concentrations caused the inhibition of histamine release induced by substance P. This inhibitory effect was not observed in PMC from male rats (Figure 2). In PMCs from female rats, pretreatment with E2 starting at 10 pM up to 10 nM significantly inhibited the substance P-induced histamine release from 27 ± 3.2% (mean release induced by substance P alone) to 12.25 ± 1.3% (release induced by substance P after preincubation with the hormone at the indicated concentrations). P4 at all the concentrations used (from 10 pM to 100 nM) significantly inhibited the histamine release induced by substance P from 28.13 ± 2.3% to values ranging from 11.3 to 13.9%. A slightly inhibitory effect was observed when PMCs from male rats were pretreated with 100 nM P4; however, it was not significantly different from the same cells treated with substance P alone (Figure 2). Pretreatment with T4 and DTH also induced significant inhibition of histamine secretion, on PMCs from female rats, at all the concentrations used; in those cases, levels of histamine release induced by substance P were reduced about 10%. Interestingly, while pretreatment of PMCs from male rats with estradiol, progesterone, and testosterone did not affect the histamine release stimulated by substance P, pretreatment of the same cells with DHT potentiated the histamine release in a dose- and gender-dependent manner. Indeed, DHT pretreatment increased histamine secretion in the male rat PMCs significantly from 33.34 ± 3.4% to 41.55 ± 2.7 (10 pM DHT) and 46.8 ± 3.1 (100 nM DHT).


Gender-related effects of sex steroids on histamine release and FcεRI expression in rat peritoneal mast cells.

Muñoz-Cruz S, Mendoza-Rodríguez Y, Nava-Castro KE, Yepez-Mulia L, Morales-Montor J - J Immunol Res (2015)

Effect of gender and sex steroid concentration on histamine release induced by substance P in mast cells. Rat PMCs were pretreated with E2, P4, T4, and DHT at 10 pM to 10 nM for 90 min at 37°C, followed by 30 min incubation with 10 μM of substance P. Values are means ± SEM of three independent experiments in triplicate. *P < 0.05, **P < 0.01, and ***P < 0.001 with and without hormone. Comparisons between genders were performed by one-way analysis of variance (ANOVA), followed by Bonferroni's multiple comparison test (GraphPad Prism). Hormone concentration and gender had significant effect and the interaction is statistically significant (P < 0.001).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4417946&req=5

fig2: Effect of gender and sex steroid concentration on histamine release induced by substance P in mast cells. Rat PMCs were pretreated with E2, P4, T4, and DHT at 10 pM to 10 nM for 90 min at 37°C, followed by 30 min incubation with 10 μM of substance P. Values are means ± SEM of three independent experiments in triplicate. *P < 0.05, **P < 0.01, and ***P < 0.001 with and without hormone. Comparisons between genders were performed by one-way analysis of variance (ANOVA), followed by Bonferroni's multiple comparison test (GraphPad Prism). Hormone concentration and gender had significant effect and the interaction is statistically significant (P < 0.001).
Mentions: The neuropeptide substance P was used to analyze the effect of sex hormones on histamine released induced by a classic MC secretagogue. Pretreatment of PMCs from female rats with E2, P4, T4, and DHT at physiological concentrations caused the inhibition of histamine release induced by substance P. This inhibitory effect was not observed in PMC from male rats (Figure 2). In PMCs from female rats, pretreatment with E2 starting at 10 pM up to 10 nM significantly inhibited the substance P-induced histamine release from 27 ± 3.2% (mean release induced by substance P alone) to 12.25 ± 1.3% (release induced by substance P after preincubation with the hormone at the indicated concentrations). P4 at all the concentrations used (from 10 pM to 100 nM) significantly inhibited the histamine release induced by substance P from 28.13 ± 2.3% to values ranging from 11.3 to 13.9%. A slightly inhibitory effect was observed when PMCs from male rats were pretreated with 100 nM P4; however, it was not significantly different from the same cells treated with substance P alone (Figure 2). Pretreatment with T4 and DTH also induced significant inhibition of histamine secretion, on PMCs from female rats, at all the concentrations used; in those cases, levels of histamine release induced by substance P were reduced about 10%. Interestingly, while pretreatment of PMCs from male rats with estradiol, progesterone, and testosterone did not affect the histamine release stimulated by substance P, pretreatment of the same cells with DHT potentiated the histamine release in a dose- and gender-dependent manner. Indeed, DHT pretreatment increased histamine secretion in the male rat PMCs significantly from 33.34 ± 3.4% to 41.55 ± 2.7 (10 pM DHT) and 46.8 ± 3.1 (100 nM DHT).

Bottom Line: Our results demonstrated that effect of sex steroids on MCs histamine release is dose- and gender-dependent and can be direct, synergistic, or inhibitory depending on whether hormones are used alone or to pretreat MCs followed by substance P-stimulation or upon IgE-mediated stimulation.In contrast, sex steroids did not have effect on the MC expression of the IgE high affinity receptor, FcεRI, no matter female or male rats were used.In conclusion, MCs degranulation is modulated by sex hormones in a gender-selective fashion, with MC from females being more susceptible than MC from males to the effects of sex steroids.

View Article: PubMed Central - PubMed

Affiliation: Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, Instituto Mexicano del Seguro Social, 06720 México, DF, Mexico.

ABSTRACT
Mast cells (MCs) are versatile effector and regulatory cells in various physiologic, immunologic, and pathologic processes. In addition to the well-characterized IgE/FcεRI-mediated degranulation, a variety of biological substances can induce MCs activation and release of their granule content. Sex steroids, mainly estradiol and progesterone, have been demonstrated to elicit MCs activation. Most published studies have been conducted on MCs lines or freshly isolated peritoneal and bone marrow-derived MC without addressing gender impact on MC response. Our goal was to investigate if the effect of estradiol, progesterone, testosterone, and dihydrotestosterone (DHT) on MCs may differ depending on whether female or male rats are used as MCs donors. Our results demonstrated that effect of sex steroids on MCs histamine release is dose- and gender-dependent and can be direct, synergistic, or inhibitory depending on whether hormones are used alone or to pretreat MCs followed by substance P-stimulation or upon IgE-mediated stimulation. In contrast, sex steroids did not have effect on the MC expression of the IgE high affinity receptor, FcεRI, no matter female or male rats were used. In conclusion, MCs degranulation is modulated by sex hormones in a gender-selective fashion, with MC from females being more susceptible than MC from males to the effects of sex steroids.

No MeSH data available.


Related in: MedlinePlus