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Biological Chemistry

Hormones could help explain lower rates of asthma in men

Testosterone keeps inflammation-inducing lung cells in check, study shows

by Tien Nguyen
November 30, 2017 | APPEARED IN VOLUME 95, ISSUE 48

Credit: Shutterstock
Women tend to have more severe cases of asthma than men.

Women are twice as likely as men to be afflicted by asthma, the airway constricting condition that can range from annoying to life-altering.

Before puberty, however, the trend is reversed: Young boys are more likely to have asthma than girls. The reasons behind the sex-based switch remain “enigmatic,” says Darryl Zeldin, an asthma expert at the National Institute of Environmental Health Sciences, but scientists suggest that the shift may be connected to changes in sex hormones.

A new study, led by Dawn C. Newcomb at Vanderbilt University Medical Center, provides a potential molecular mechanism (Cell Rep. 2017, DOI: 10.1016/j.celrep.2017.10.110). Newcomb and coworkers examined the effect of sex hormones on lung cells, called group 2 innate lymphoid (ILC2) cells, that have been linked to asthma in recent years. The cells produce proteins that initiate the inflammation and mucus buildup that make it hard for people with asthma to breathe.

The researchers tested blood samples from men and women with and without asthma. They found that people with asthma possessed more ILC2 cells and that women with asthma had more of these cells than men with asthma. In mouse studies, the team observed that testosterone suppressed ILC2 cells’ expansion and activity, whereas estrogen and progesterone had no effect.

Understanding sex differences in asthma is important when choosing patients for clinical trials, Newcomb says. Patients with severe asthma—typically women—don’t always respond to standard treatments like corticosteroid inhalers, Newcomb says, so new therapies are needed.

“Currently there are no treatments for asthma that target sex hormone signaling pathways,” Zeldin says, adding that the beneficial effects of testosterone and its related analogs may represent a novel approach for the treatment of this type of lung inflammation for both sexes.

Newcomb stresses that hormones are one of many factors—including genetics, infections, and the environment—that can influence the development of asthma.

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