Effects of estrogen on bronchial hyperresponsiveness of ovariectomized murine tracheal rings sensitized with human asthmatic serum.

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Exogenous estrogen or increased estrogen levels in pregnancy decrease asthma severity, suggesting that sex hormones may modulate the frequency and severity of asthma exacerbations and raising the possibility that estrogen may affect airway smooth muscle function and hyper-responsiveness in asthma. Therefore, we studied the effects of estrogen replacement therapy on carbachol-induced constriction of mouse tracheal rings. Female mice were ovariectomized (OVX) and implanted subcutaneously with an estrogen pellet releasing either 5μg or 15μg estradiol/day. After the 3 weeks estrogen treatment, animals were sacrificed and tracheal rings were sensitized overnight in medium containing serum from asthmatic (IgE> 1,000U) or non asthmatic (IgE <70U) humans and used for tension studies. The maximal contractile force (Fmax) to carbachol in rings from OVX mice sensitized with serum from asthmatic patients (ATR) was much higher than the Fmax in ATR from OVX mice receiving estrogen replacement and similar to the Fmax of ATR from male mice. In male mice, Fmax to carbachol in tracheal rings treated with serum from control patients (CTR) was 3.8±0.6g, compared to 6.1 ± 1.0g in ATR from male mice and 5.6±0.9g in ATR from female OVX mice. Conversely, Fmax to carbachol was 2.4 ± 0.3g in ATR from female OVX mice treated with 5μg estradiol/day and 2.7 ± 0.4 g in ATR from female OVX mice treated with 15μg estradiol/day. These results indicate that ovariectomized female mice are more susceptible to the asthmatic phenotype than ovariectomized female mice receiving estrogen replacement therapy, and suggest a protective role of estrogen replacement therapy in asthma.