Anyone who has ever said they were scared to the bone may have spoken more literally than we knew. A new study on Thursday appears to show that in mice and humans, bones release hormone in response to stress. What's more, this bone hormone seems crucial to our fight-or-flight response, in a way completely separate from other well-known stress chemicals like adrenaline.
Gerard Corsenti, a Columbia University geneticist, and his colleagues have long been interested in studying how our skeleton keeps us alive and well – not only by supporting us physically, but also by the interactions it has with the rest of the body. Their work is focused on osteocalcin, a hormone produced by some of the same cells that make up bone. His and other earlier studies indicate that osteocalcin helps regulate various functions such as metabolism, muscle function during exercise and fertility.
"What we have found is that you do not necessarily need an ounce of the adrenal glands to produce this acute stress response, at least in mice.
In this sense, osteocalcin acts similarly to other hormones produced by the glands and organs that make up our endocrine system. Therefore, Corsenti and his team argue that the skeleton should be considered an endocrine organ. This way of thinking has led the Karsenty team to theorize that our skeletons can evolve to help us better respond to stress, as this is another major function of the endocrine system. And if so, then osteocalcin should play a leading role there as well.
To test this theory, they first experimented with mice. They exposed poor rodents to various sources of acute stress, such as restricting or causing them to suppress the fox's urine, a common predator. Judging by their blood tests, the team found that stressed mice produced more osteocalcin within minutes of their test.
Then they pass on to people. But since fox urine does not have exactly the same effect on us, Karsenty instead asked volunteers to make some public speeches and then ask questions. As expected, people's blood pressure and heart rate increased, as did osteocalcin levels.
The team's findings were published on Thursday on cell metabolism.
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Other genetic experiments in mice suggest that osteocalcin directly affects a part of the brain called the amygdala, a region known for helping us process emotions like fear. But the important thing is that this path from our bones to our brains does not seem to include the adrenal glands – the organ located above our kidneys, long considered the key to responding to the fight or flight.
It may even be that osteocalcin is more important in igniting a fire under our danger than our adrenal glands. In mice bred as unable to respond to osteocalcin, their struggle or flight response was dramatically silenced, but the same was not true when the mice lacked adrenal glands. These mice were still capable of feeling quickly stressed.
"What we've found is that you don't necessarily need an ounce of adrenal glands to produce this acute stress response, at least in mice," says Karsenti. "And that may explain why even people without adrenaline can still have an intact answer."
In Karsenty's theory, adrenaline and other hormones are not useless in our fight or flight response. On the one hand, some of our nerve cells produce adrenaline and a related hormone called norepinephrine, too. His team believes that osteocalcin production triggers the release of these hormones in the brain, which then regulate other aspects of our acute stress response. Our adrenal glands probably still play their own role, even if they are not the starting gun that sends us when we spot a tiger in the grass or a spider on the wall.
There is still much work that needs to be done before we can rewrite the book on stress and adrenaline. This will include additional experiments with other test animals as well as humans. But if nothing else, this is the latest study to show that the body is even more complex and interconnected than we thought it was.
"We do not study the body for as long as people think. We are studying groups of cells isolated from each other, "said Carsenti. "But what mouse genetics now allows is to look at organ function and how hormones and molecules mediate their function throughout a complex organism."