Discovery of Sex Hormone Yields Clues Into Disease Treatments

“We were interested in trying to discover new ways to inhibit inflammation in the brain [so we] looked into whether the drugs were mimicking activities of natural hormones that might be in the brain,” Glass said. “We went searching and we ended up finding a natural steroid called ADIOL that has many properties of drugs we tested.”

Cells of the sex hormones androgen and estrogen eventually mature into these newly discovered ADIOL cells, which regulate inflammation caused by microglia cells that help the central nervous system respond to infections and injuries.

Microglia cells in the nervous system are watchdogs that look out for invading microbes or tissue damage. When they find something, these cells start up an inflammatory response in the immune system and begin to repair tissues. However, if the inflammatory response is not controlled or continues for a long period, neurons can be damaged or die.

Researchers found that this microglia inflammation is regulated by the production of ADIOL, which tells supporting cells to ease up and return to their resting state. The hormone works by binding to estrogen receptor beta to generate an anti-inflammatory response to the two cell types in the nervous system. As a result, estrogen cannot bind and can get in the way of ADIOL.

“[We] tested a large series of synthetic molecules that can bind to this estrogen receptor beta and we found that some of them were blocking inflammation,” Glass said.

This discovery can indicate that women are more prone to inflammatory diseases like multiple sclerosis because they have more estrogen in their bodies. In addition, it can explain some of the severe effects of administering estrogen to the brain for post-menopausal women.

“Many aspects of inflammation one can observe in multiple sclerosis are also see in other types of neurodegenerative diseases,” Glass said. “People are beginning to see that inflammation is contributing to the severity of the disease, so an idea — and it’s not just our idea, lots of people have this idea — is that by inhibiting inflammation in the brain, we might be able to slow down the development of these very debilitating degenerative diseases.”

Levels of the hormone in the body can be helpful in predicting responses to drugs that mimic its actions.

Glass and his team of researchers will continue to study ADIOL further, such as finding out how much is naturally produced in each individual and discerning the relationship between brain inflammation and neurodegenerative disease.

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