Tuning The 'Fight-Or-Flight ' Response: Molecular Memory Of Stress Prompts Adrenaline Surges, Cornell Study Shows

Now Cornell University neurobiologists, studying the adrenal glands of rats, have discovered how chronic stress cranks up the intensity of this adrenaline response. The key to this so-called molecular memory resides in a donut-shaped protein on the surface of cells that secrete adrenaline, the hormone also known as epinephrine.

"The hormonal response to stress is different for every individual, and seems to be controlled by some combination of inheritance and lifestyle," explains David P. McCobb, co-author along with Jiuyong Xie of a report in the April 17 issue of the journal Science. "Our study points to the effect of lifestyle. Stressful experience is remembered, and biases us toward responding forcefully to subsequent threats," McCobb says.

Improved understanding of chemical signaling cascades in the endocrine system could lead to better medical therapies -- perhaps even gene therapy -- for conditions such as hypertension and heart attack, predict McCobb, an assistant professor of neurobiology and behavior, and Xie, a postdoctoral researcher in the McCobb's department.

"Whether our stress responses are controlled by genes or lifestyle, we'd like to have more control," McCobb says. "We don't want to secrete more adrenaline than necessary. There's a definite adaptive advantage to being able to back off."

The Cornell researchers report that adrenal cells dump adrenaline into the blood at a rate that is determined not only by the necessary incoming neural signals from the brain, but also by the intrinsic electrical excitability of the adrenal cells themselves. That excitability is determined by the structural detail of the donut-shaped channel proteins that allow potassium electrical signals to cross the cell membrane. And the structural detail is controlled at the gene level by steroids, according to the researchers.

Forceful heart, lung, metabolic and behavioral reactions help cope with acute threats, McCobb says, "but those reactions are not healthful in the long run. We found that steroid stress hormones dictate whether the potassium channels controlling adrenaline release are constructed with or without an optional piece called STREX, for stress exon. This STREX exon causes the channel to open more easily, which favors rapid, excitable responses and fast secretion of adrenaline."

To test the theory, the Cornell researchers surgically removed several rats' pituitary glands, the source of ACTH (adrenocorticotropic hormone), a key link in the stress hormone cascade. Without pituitary glands, the percentage of STREX-type channels dropped sharply. This was prevented by injecting ACTH artificially.

The Science article is entitled, "Control of Alternative Splicing of Potassium Channels by Stress Hormones."