The idea that females are more resilient than males in
responding to stress is a popular view, and now University at Buffalo
researchers have found a scientific explanation.
"We have examined the molecular mechanism underlying
gender-specific effects of stress," says senior author Zhen Yan, PhD, a
professor in the Department of Physiology and Biophysics in the UB School of
Medicine and Biomedical Sciences. "Previous studies have found that
females are more resilient to chronic stress and now our research has found the
The research shows that in rats exposed to repeated episodes
of stress, females respond better than males because of the protective effect
of oestrogen. In the UB study, young female rats exposed to one week of
periodic physical restraint stress showed no impairment in their ability to
remember and recognise objects they had previously been shown. In contrast,
young males exposed to the same stress were impaired in their short-term
How the study was
An impairment in the ability to correctly remember a
familiar object signifies some disturbance in the signalling ability of the
glutamate receptor in the prefrontal cortex, the brain region that controls
working memory, attention, decision-making, emotion and other high-level
Last year, Yan and UB colleagues published in Neuron a paper showing that repeated
stress results in loss of the glutamate receptor in the prefrontal cortex of
The current paper shows that the glutamate receptor in the
prefrontal cortex of stressed females is intact. The findings provide more
support for a growing body of research demonstrating that the glutamate
receptor is the molecular target of stress, which mediates the stress response.
The stressors used in the experiments mimic challenging and stressful, but not
dangerous, experiences that humans face, such as those causing frustration and
feelings of being under pressure, Yan says.
By manipulating the amount of oestrogen produced in the
brain, the UB researchers were able to make the males respond to stress more like
females and the females respond more like males.
"When oestrogen signalling in the brains of females was
blocked, stress exhibited detrimental effects on them," explains Yan.
"When oestrogen signalling was activated in males, the detrimental effects
of stress were blocked.
"We still found the protective effect of oestrogen in
female rats whose ovaries were removed," says Yan. "It suggests that
it might be oestrogen produced in the brain that protects against the
detrimental effects of stress." In the current study, Yan and her
colleagues found that the enzyme aromatase, which produces estradiol, an oestrogen
hormone, in the brain, is responsible for female stress resilience. They found
that aromatase levels are significantly higher in the prefrontal cortex of female
"If we could find compounds similar to oestrogen that
could be administered without causing hormonal side effects, they could prove
to be a very effective treatment for stress-related problems in males,"
she says. She notes that while stress itself is not a psychiatric disorder, it
can be a trigger for the development of psychiatric disorders in vulnerable