Differences in biological sex can dictate lifelong disease patterns, says a new study by the researchers that links connections between specific hormones present before and after birth with immune response and lifelong immunological disease development.
Published in the most recent edition of the Proceedings of the National Academy of Sciences, the study answers questions about why females are at increased risk for common diseases that involve or target the immune system like asthma, allergies, migraines and irritable bowel syndrome. The findings also open the door for new therapies and preventatives
"This research shows that it's our perinatal hormones, not our adult sex hormones, that have a greater influence on our risk of developing mast cell-associated disorders throughout the lifespan," says the study's principle investigator. "A better understanding of how perinatal sex hormones shape lifelong mast cell activity could lead to sex-specific preventatives and therapies for mast cell-associated diseases."
Mast cells are white blood cells that play beneficial roles in the body. They orchestrate the first line of defense against infections and toxin exposure and play an important role in wound healing, according to the study.
However, when mast cells become overreactive, they can initiate chronic inflammatory diseases and, in certain cases, death. Prior research from the group linked psychological stress to a specific mast cell receptor and overreactive immune responses.
They also previously discovered sex differences in mast cells. Female mast cells store and release more inflammatory substances like proteases, histamine and serotonin, compared with males. Thus, female mast cells are more likely than male mast cells to kick-start aggressive immune responses. While this may offer females the upper hand in surviving infections, it also can put females at higher risk for inflammatory and autoimmune diseases.
The latest research explains why these sex-biased disease patterns are observed in both adults and prepubertal children. They found that lower levels of serum histamine and less-severe anaphylactic responses occur in males because of their naturally higher levels of perinatal androgens, which are specific sex hormones present shortly before and after birth.
"Mast cells are created from stem cells in our bone marrow," the author said. "High levels of perinatal androgens program the mast cell stem cells to house and release lower levels of inflammatory substances, resulting in a significantly reduced severity of anaphylactic responses in male newborns and adults."
"We then confirmed that the androgens played a role by studying males who lack functional androgen receptors," says another author.
While high perinatal androgen levels are specific to males, the researchers found that while in utero, females exposed to male levels of perinatal androgens develop mast cells that behave more like those of males.
"For these females, exposure to the perinatal androgens reduced their histamine levels and they also exhibited less-severe anaphylactic responses as adults," says the lead author.
In addition to paving the way for improved and potentially novel therapies for sex-biased immunological and other diseases, future research based will help researchers understand how physiological and environmental factors that occur early in life can shape lifetime disease risk, particularly mast cell-mediated disease patterns.
"While biological sex and adult sex hormones are known to have a major influence on immunological diseases between the sexes, we're learning that the hormones that we are exposed to in utero may play a larger role in determining sex differences in mast cell-associated disease risk, both as adults and as children," the senior author said.
Connecting hormones we're born with to lifetime risk for immunological diseases
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