Stress Hormone Causes Epigenetic Changes

Stress Hormone Causes Epigenetic Changes | National Institutes of Health (NIH) – September 27, 2010

Researchers found that chronic exposure to a stress hormone causes modifications to DNA in the brains of mice, prompting changes in gene expression. The new finding provides clues into how chronic stress might affect human behavior.

And how about the chronic stress from living with constant pain? And never being able to plan ahead because it’s impossible to know how much pain any day or time will bring, impossible to know what you’ll be capable of at any specific time?

What about the stress of being disabled from earning a paycheck and making a living, of having to rely on government handouts and the generosity of family and friends?

And, to top it off, always having to worry whether your doctor will continue prescribing opioids or leave you to suffer the endless torture without relief? 

During stressful situations, we produce steroid hormones called glucocorticoids that affect many systems throughout the body.

These effects are mediated by the hypothalamic-pituitary-adrenal (HPA) axis, a network involving the hypothalamus and pituitary gland in the brain and the adrenal glands near the kidneys.  

Past studies have found that glucocorticoids alter gene expression in the brain.

The researchers added corticosterone—the major hormone that mice produce in stressful situations—to their drinking water for 4 weeks.

After exposure, and again after a 4-week recovery period without corticosterone, the scientists tested the mice for behavioral and physiological changes.

They examined the expression levels of 5 HPA axis genes in the hippocampus, hypothalamus and blood.

They also tested the genes’ methylation levels—a common epigenetic modification that affects gene expression.

In the September 2010 issue of Endocrinology, the researchers reported that mice given corticosterone appeared more anxious during a maze test. Chronic exposure to corticosterone altered the expression of 3 HPA axis genes, including higher levels of Fkbp5 in the hippocampus, hypothalamus and blood.

Genetic variations in Fkbp5 have been associated with posttraumatic stress disorder and mood disorders, which are characterized by abnormal glucocorticoid regulation. These results suggest that methylation of Fkbp5 may play a role in mediating the effects of glucocorticoids on behavior.

Epigenetic marks added to DNA through life experience may prepare an animal for future events, he explains. “If you think of the stress system as preparing you for fight or flight, you might imagine that these epigenetic changes might prepare you to fight harder or flee faster the next time you encounter something stressful.”

With modern stressors, such as work deadlines, we can’t fight or flee, and chronic stress may instead lead to depression or other mood disorders.

Understanding the mechanism by which chronic stress leads to these conditions might help us find new ways to prevent or treat them in the future. This research suggests that epigenetic changes could play a role in the process.

However, it’s important to note that the connection is still speculative. Future studies will be needed to better understand the effects of chronic stress.

And below is a “future study” from 2 years later:

Molecular Effects of Social Stress | National Institutes of Health (NIH) – April 23, 2012

Social rank has broad effects on gene regulation, particularly in the immune system, according to a new study in rhesus macaques.

A growing body of evidence suggests that the stress of a low social ranking can also influence mental and physical health in a variety of ways.

These include suppressed immune function and elevated risk for cardiovascular problems like hypertension, heart disease and stroke.

In the new study, researchers investigated whether social status affects gene regulation.

The researchers examined social groups of female rhesus macaques. In the wild, female macaques generally inherit their social rank from their mothers and stay in the social group they were born into

The team identified almost 1,000 genes whose expression levels varied with social rank.

• Over 500 were more highly expressed in high-ranking macaques;
• about 450 were more highly expressed in low-ranking animals.
• The largest functional group, with 112 genes, related to the immune system.

The researchers found that, by looking at these expression levels, they could correctly predict social rank for 80% of the macaques they tested.

The social status of 7 macaques changed during the study, giving the scientists an opportunity to confirm that gene expression changes with social rank. They found that gene expression levels could correctly determine the social rank of 6 out of the 7 females.

They found that the DNA methylation differences were modest but corresponded with expression. The finding provides at least a partial explanation for how the body might quickly change expression in response to social rank.

“There’s a spooky side to this kind of research, in that an individual’s social rank is partially determining health status,” Tung says.