Mayo ClinicThe role played by sex steroids in modulating airway tone seems to have caught the attention of researchers from the Mayo Clinic. Female sex hormones as per a new bench research could work with beta-agonists in reducing airway constriction.

Post puberty, women seem to have a tendency to exhibit worse asthma symptoms and exacerbations in comparison to men. Interestingly women were also discovered to experience changes in airway reactivity in the course of their menstrual cycle, with pregnancy, and at the onset of menopause.

“Given these clinical observations, it is of interest to determine whether sex steroids (estrogen, progesterone) play a role in modulating airway tone,” mentioned lead student researcher, Elizabeth A. Townsend, of the Mayo Clinic Department of Physiology and Biomedical Engineering, where she is completing her Ph.D. “What is less clear is whether sex steroids, especially estrogens, are detrimental or beneficial to airway function.”

“Increased bronchoconstriction, as in asthma, is directly influenced by the amount of intracellular calcium in airway smooth muscle. Therefore, we set out to explore the effect of estrogens on calcium regulation in airway smooth muscle. Calcium regulation is a key factor in determining bronchoconstriction” further says Ms. Townsend. “Since asthma symptoms have been documented to be worst when estrogen levels are lowest in the late luteal phase, we hypothesized that estrogens facilitate bronchodilation, rather than constriction.”

The hypothesis was tested by exposing human airway smooth muscle tissue and cells isolated from surgical lung samples to small doses of estradiol. These were known to be comparable to physiologic levels noticed in women. It was uncovered that acute exposure namely about 15 minutes to estradiol at concentrations that may be pitted against those experienced during a woman’s menstrual cycle reduced intracellular calcium in airway smooth muscle cells.

Moreover, in small quantities, estradiol significantly reduced force production by human airways that had been stimulated with bronchoconstrictors. This apparently points at augmented bronchodilation causing Townsend and colleagues to question if estrogens could produce bronchodilation. They also asked whether the combination of commonly used bronchodilators (β2 agonists) and estrogens be used to generate even larger bronchodilation?

Employing human airway smooth muscle cells in laboratory studies, the researchers discovered that combined treatment with estradiol and the β-agonist, isoproterenol (which non-selectively activates both β1 and β2 adrenergic receptors), appeared to have a synergistic effect on lowering intracellular calcium and force. It was found to be more than either estradiol or isoproterenol alone. Also these effects could involve a common signaling pathway as per the research.

“These novel data suggest that estradiol has bronchodilatory properties, and may potentiate β2-agonist effects,” further sahres Ms. Townsend. “The finding that estrogens interact synergistically with β-adrenoceptor signaling (perhaps using common pathways) to facilitate bronchodilation was exciting, and lends itself to further studies on interactions between sex steroids and β2-agonists”.

The researcher and her team cautions that there may still be considerable finding necessary to better comprehend the relation between sex steroids and factors that could contribute to asthma. Only then can the information probably be used clinically in patients to relieve asthma symptoms.

The findings will be presented at the ATS 2010 International Conference in New Orleans.