The fight or flight response was previously thought to be triggered by the hormone adrenaline, but new research suggests the bone-derived hormone osteocalcin is the first to flip the alarm switch.

"In bony vertebrates, the acute stress response is not possible without osteocalcin," Dr. Gérard Karsenty, chair of the department of genetics and development at Columbia University Vagelos College of Physicians and Surgeons, said in a news release. "It completely changes how we think about how acute stress responses occur."

Research conducted by Karsenty and his colleagues suggests the skeletal system can influence the functionality and biochemistry of other organs, including the pancreas, brain and muscles, through the release of osteocalcin.

During an earlier study, Karsenty and his research partners showed osteocalcin helps animals alter their metabolism to allow cells to absorb more glucose, boosting memory and helping animals run faster with greater endurance.

When researchers asked themselves why bones can have this effect on animal physiology, their attention turned to the ever-present need to escape danger.

"If you think of bone as something that evolved to protect the organism from danger -- the skull protects the brain from trauma, the skeleton allows vertebrates to escape predators, and even the bones in the ear alert us to approaching danger -- the hormonal functions of osteocalcin begin to make sense," Karsenty said.

For the latest study, scientists designed tests to determine whether osteocalcin works fast enough to assume responsibility for the fight or flight response. In the lab, researchers exposed mice to the urine of a predator. Within two to three minutes, osteocalcin levels spiked.

The stress of public speaking or cross-examination produced similar osteocalcin spikes in the

bloodstreams of humans.

In mice, the osteocalcin spike was followed by increases in heart rate, body temperature and blood glucose levels.

In subsequent tests, scientists disabled the production and reception of osteocalcin in several mice specimens. Exposure to the urine of a predator failed to trigger an acute stress response in the rodents.

While adrenaline can help magnify or assist in the production of a stress response, previous studies have shown both animals and humans without the ability to produce adrenaline can have a stress response. The latest research helps explain why.

"This shows us that circulating levels of osteocalcin are enough to drive the acute stress response," said Karsenty.

Researchers suggest their findings -- published this week in the journal Cell Biology -- are just one of example of a new frontier in science made possible by advances in genetic testings. Scientists anticipate new studies will reveal the heart and muscles to have similarly important influences on the functionality and biology of other organs.

"I have no doubt that there are many more new inter-organ signals to be discovered, and these interactions may be as important as the ones discovered in the early part of the 20th century," Karsenty said.

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