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ABSTRACT
Background: Use of hormone replacement therapy (HRT) may increase the risk of adult-onset asthma in women. Various in vitro studies have reported that estradiol stimulates human mast cell lines causing release of allergic mediators which was not observed in estrogen receptor-α (ER-α) knockout mice. Thus, estrogen might be a key element in occurrence of asthma. In the present study, we proposed to determine the role of ER-α in an experimental model of bronchial asthma. Methods: Trypsin and egg albumin induced chronic model of asthma were used. On the 28^sup th^ day, various parameters such as pO^sub 2^ level, serum bicarbonate level, tidal volume, respiratory rate, air flow rate, differential white blood cells count in the bronchoalveolar lavage (BAL) fluid and serum cholesterol level were measured as well as lung histopathological examination and uterine weight measurement were carried out. Results: Estradiol treatment resulted in lower pO^sub 2^ level, tidal volume and air flow rate. Also, serum bicarbonate level, respiratory rate and eosinophil rate and eosinophil count in BAL fluid were higher as compared to asthmatic control group. These effects were not observed in methyl-piperidino-pyrazole (MPP) co-treated group. Histopathological data suggested that the destruction of alveolar and muscular layers was more prominent in estradiol-treated group than asthmatic control and MPP co-treated groups. Estradiol-treated group showed lower total serum cholesterol levels and higher uterine weight as compared to asthmatic control group which was not observed in MPP co-treated group; indicating antagonism of estradiol by MPP at ER-α receptor. Conclusion: Estrogen seems to have a strong promoting effect on pathogenesis of bronchial asthma via ER-α receptors. Iran. Biomed. J. 14 (1 & 2): 41-48, 2010
Keywords: Estrogen receptor Alpha (ER-α), Estradiol, Asthma
Abbreviations: estrogen receptor-α (ER-α,), bronchoalveolar lavage (BAL), methyl-piperidino-pyrazole (MPP), hormone replacement therapy (HRT), 17-β-E^sub 2^ methyl-piperidino-pyrazole (17-β-estradiol), methyl-piperidino-pyrazole (MPP), hormone replacement therapy (HRT)
INTRODUCTION
Asthma is defined as a chronic inflammatory disorder of the airway, characterized by reversible airflow obstruction causing cough, wheeze, chest tightness and shortness of breath. Inflammation of the bronchial wall involving eosinophils, mast cells and lymphocytes together with the cytokine and inflammatory products of these cells induces hyper-responsiveness of the bronchi so that they narrow more readily in response to a wide range of stimuli [1]. The prevalence and morbidity of...