Who ever said they felt afraid of their legs could have spoken more literally than we knew. A new study on Thursday seems to show that both mice and humans secrete a hormone in response to stressful situations. In addition, this bone hormone seems crucial to our fight-or-flight response, in a way that is completely separate from other well-known stress chemicals such as adrenaline.
Gerard Karsenty, a geneticist at Columbia University, and his colleagues have long been interested in studying how our skeleton keeps us alive and healthy – not just by supporting us physically, but by the interactions it has with the rest of the body. Their work has focused on osteocalcin, a hormone produced by some of the same bone-forming cells. His and others' previous research has suggested that osteocalcin helps regulate various functions such as metabolism, muscle function during exercise and fertility.
"What we found is that you do not necessarily need an ounce in the adrenal glands to produce this acute stress response, at least in mice."
In this regard, osteocalcin works much like other hormones produced by the glands and organs that make up our Because of this, Karsenty and his team have argued that the skeleton should be considered a hormone organ, which led Karsenty's team to theorize that our skeletons could have been developed to help us respond better to stress, as it is another important function of the endocrine system, and if so, osteocalcin should also play a leading role there.
To test this theory, they first experimented with mice, exposing the poor rodents to various sources of acute stress, for example. by restricting them or letting them sniff urine from foxes, a common predator. Based on their blood tests, the team found that stressed mice ss produced more osteocalcin within minutes of their trial.
They then moved on to people. But since the fox didn't have the same effect on us, Karsenty instead asked volunteers to do some public speaking and then take questions. As expected, people's blood pressure and heart rate increased, as did their levels of osteocalcin.
The team's results were published on Thursday in cell metabolism.
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Other genetic experiments in mice suggested that osteocalcin directly affects a part of the brain called the amygdala, a region well known for helping us process emotions such as fear. But it is important that this path from our bones to our brains does not seem to involve the adrenal glands – the organ that is located above our kidneys, long seen as the key to the fight-or-flight response.
It may even prove that osteocalcin is more important to light a fire under us before the danger than our adrenal glands are. In mice bred to be unable to respond to osteocalcin, their fight-or-flight response was drastically attenuated, but the same was not true when mice lacked the adrenal glands. These mice could still feel stressed.
"What we found is that you don't necessarily need an ounce in the adrenal glands to produce this acute stress response, at least in mice," Karsenty said. "And this may explain why even people without adrenaline can still have an intact response."
In Karsenty's theory, adrenaline and other hormones are not worthless for our fight-or-flight response. First, some of our nerve cells produce adrenaline and a related hormone called norepinephrine. His team believes that the production of osteocalcin triggers the release of these hormones in the brain, which then regulates other aspects of our acute stress response. Our adrenal glands probably still play their own role, although they are not the launching gun that sends us when we see a tiger in the grass or a spider on the wall.
There is still much work to be done before we can write about the book on stress and adrenaline. It will involve further experiments with other test animals and humans. But if nothing else, this is the latest research that shows that the body is even more complicated and interconnected than we have assumed it to be.
"We have not studied the body as long as people believe. We have studied groups of cells, isolated from each other, "Karsenty said. "But what mouse genetics now allow is that we can look at the function of organs, and how hormones and molecules mediate their function, in a whole complex organism."