Estrogens and asthma

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Estrogen May Reduce Airway Constriction in Women Patients With Asthma

ScienceDaily (May 18, 2010) — Female sex hormones may work with beta-agonists in

reducing airway constriction, according to new bench research from the Mayo

Clinic.

The findings are being presented at the ATS 2010 International Conference in New

Orleans.

After puberty, women tend to have worse asthma symptoms and exacerbations than

men. Women also experience changes in airway reactivity throughout 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, " said

lead student researcher, 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 "

said 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. "

To test this hypothesis, Ms. Townsend and colleagues exposed human airway smooth

muscle tissue and cells isolated from surgical lung samples to small doses of

estradiol comparable to physiologic levels found in women. They found that acute

(15 minute) exposure to estradiol at concentrations comparable to those

experienced during a woman's menstrual cycle decreased intracellular calcium in

airway smooth muscle cells. Furthermore, small amounts of estradiol

significantly decreased force production by human airways that had been

stimulated with bronchoconstrictors, indicating increased bronchodilation.

Townsend and colleagues then asked whether estrogens could produce

bronchodilation, and might the combination of commonly used bronchodilators

(beta-2 agonists) and estrogens be used to produce even greater bronchodilation?

In laboratory studies using human airway smooth muscle cells, they found that

combined treatment with estradiol and the beta-agonist, isoproterenol (which

non-selectively activates both beta-1 and beta-2 adrenergic receptors), had a

synergistic effect on decreasing intracellular calcium and force more than

either estradiol or isoproterenol alone. They also found that these effects may

involve a common signaling pathway.

" These novel data suggest that estradiol has bronchodilatory properties, and may

potentiate beta-2-agonist effects, " said Ms. Townsend. " The finding that

estrogens interact synergistically with beta-adrenoceptor signaling (perhaps

using common pathways) to facilitate bronchodilation was exciting, and lends

itself to further studies on interactions between sex steroids and

beta-2-agonists. " But she and her team also cautioned that there is still

considerable research necessary to fully understand the association between sex

steroids and factors that contribute to asthma, before the information can be

used clinically in patients to relieve asthma symptoms.

" Our work has only focused on the acute exposure of estrogens and the observed

dilatory effects, " said Ms. Townsend. " In other organ systems and disease

states, estrogens can have complex effects on inflammation, cell signaling and

other factors also important in asthma and airway inflammation. Given our

findings, we can ask a number of questions to guide future research: what is the

effect of chronic exposure to estrogens on airway smooth muscle tone? Are there

interactions between estrogen and progesterone in the airway? Are men and women

different in their response to sex steroids in terms of airway tone? Can an

inhaled combination of beta-2-agonist and estrogen be more effective at

controlling asthma exacerbations, and potentially have a beta-2-agonist sparing

effect? "

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Adapted from materials provided by American Thoracic Society, via EurekAlert!, a

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American Thoracic Society (2010, May 18). Estrogen may reduce airway

constriction in women patients with asthma. ScienceDaily. Retrieved May 19,

2010, from http://www.sciencedaily.com /releases/2010/05/100516195531.htm