Estrogen, Stress and the Female Brain

If you suspect that women respond to stress more resiliently than men you are right, and researchers at University at Buffalo have now found out why. In rats exposed to repeated stress episodes, females respond better than males because of the protective effects of estrogen.

Before I go any further, I should mention that there are actual anatomical and developmental differences between the brain of a human male and a human female, so it is correct to use the term “female brain”. However, with all that science has recently learned about the plasticity of the brain, to say that gender behaviours are “hard-wired” into the brain would be oversimplifying at best. It is an issue that has implications for many areas, including gender assignment operations, early childhood education, and yes, stress management.

“We have examined the molecular mechanism underlying gender-specific effects of stress,” says Zhen Yan, PhD, a professor in the Department of Physiology and Biophysics at the University of Buffalo. “Previous studies have found that females are more resilient to chronic stress, and now our research has found the reason why.”

In the study, published recently in the journal, Molecular Psychiatry, young female rats exposed to one week of periodic physical restraint stress showed no impairment in ability to remember and recognize objects they had previously been shown. Young males exposed to the same stress were impaired in their short-term memory.

Prefrontal Cortex Signaling Problems

Impairment in the ability to correctly remember a familiar object denotes some trouble in the signaling ability of the glutamate receptor in the prefrontal cortex. The prefrontal cortex is the brain region that controls working memory, attention, decision-making, emotion and other high-level “executive” processes.

Zhen Yan, professor of physiology and biophysics

Zhen Yan, professor of physiology and biophysics

The researcher’s findings provide support for a growing body of research showing that the glutamate receptor is the molecular target of stress, which mediates the stress response. The stressors in the experiments modeled demanding and stressful, but not dangerous, experiences that humans face, like ones causing frustration and feelings of being under pressure, Yan said.

By tweaking levels of estrogen produced in the brain, researchers were able to make the males respond to stress more like females and the females respond more like males.

“When estrogen signaling in the brains of females was blocked, stress exhibited detrimental effects on them,” Yan says. “When estrogen signaling was activated in males, the detrimental effects of stress were blocked.”

Aromatase Estradiol Resilience

“We still found the protective effect of estrogen in female rats whose ovaries were removed,” explains Yan. “It suggests that it might be estrogen produced in the brain that protects against the detrimental effects of stress.”

The study found that the enzyme aromatase, which produces estradiol, an estrogen hormone in the brain, is responsible for female stress resilience. They found that aromatase levels are significantly higher in the prefrontal cortex of female rats.

“If we could find compounds similar to estrogen that could be administered without causing hormonal side effects, they could prove to be a very effective treatment for stress-related problems in males,” Yan says.

References:

1. Estrogen protects against the detrimental effects of repeated stress on glutamatergic transmission and cognition
J Wei, E Y Yuen, W Liu, X Li, P Zhong, I N Karatsoreos, B S McEwen and Z Yan Mol Psychiatry advance online publication, July 9, 2013; doi:10.1038/mp.2013.83

2. Morphology of the Ventral Frontal Cortex: Relationship to Femininity and Social Cognition
Jessica L. Wood, Dwayne Heitmiller, Nancy C. Andreasen, and Peg Nopoulos
Cereb. Cortex (2008) 18 (3): 534-540.doi: 10.1093/cercor/bhm079