Bones Triggers Fight-or-Flight Response, Not Adrenaline- Bizarre Discovery
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Bones Trigger Fight-or-Flight Response, Not Adrenaline- Bizarre Discovery

Hormones flood inside our bodies in preparation either for a battle or a quick escape when we face a threat, which is commonly known as the ‘fight-or-flight’ response!

For decades, we have generally thought ‘fight-or-flight’ response was driven by adrenaline hormone. But a recent study shows that one of the most important of these messengers and responses could come from a rather unexpected place i.e, our skeleton.

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We usually think of chemicals & hormones like cortisol and adrenaline as the things that get the heart racing and muscles pumping. Now the real star player could actually be osteocalcin which is a calcium-binding protein that is produced by our bones.

As a response to acute stress, steroids of the glucocorticoid variety are released by the endocrine system of our body, where these manage the production of a cascade of other ‘get ready to rumble’ chemicals throughout various tissues.

Scientists from the United States, the UK, and India argue there is one tiny problem with this explanation of the fight-or-flight reaction.

When nobody is disputing that our bodies produce cortisol when we are stressed, the fact their main action is to trigger cells into the transcribing specific genes which are a process that takes time makes it an unlikely candidate for a rapid physiological response.

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Gerard Karsenty a geneticist of Columbia University said that although this discovery certainly does not rule out that the glucocorticoid hormones may be implicated in some capacity in the acute stress response, the discovery suggests the possibility that other hormones, possibly peptide ones, could be involved. 

So Karsenty and his colleagues went on the hunt for something a little more expedient by making a discovery on Bones triggering the Fight-or-Flight Response. They did this by focussing on proteins released by bone cells that would potentially have a more immediate effect on animal metabolism.

Looking into the skeleton as a source might not be as weird as it first seems. In addition to this, our bones evolved as a way to protect our squishy bits from being squashed, either by predator or accident.

Karsenty explained that if we think of bone as something that evolved to protect the organism from danger i.e, the skull protects the brain from trauma, the skeleton also allows vertebrates to escape its predators, and also the bones in the ear alert us to approaching danger. So now the hormonal functions of osteocalcin begin to make sense.

Osteocalcin is not in any way new to science, either. We have understood its functions in bone development for nearly half a century, and in very recent years begun to suspect bone also has a hand in regulating our energy levels just by affecting glucose metabolism.

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It also seems to give an aging memory a boost, at least in lab rodents. All useful things in moments of danger.

But it is still a surprising discovery that osteocalcin might also help to kickstart our acute stress response.

Karsenty added that this discovery completely changes how we think about how acute stress responses occur.

To test their suspicions, the scientists put lab mice under duress by restraining them for a 45 minute time period. During this time, osteocalcin levels in the peripheral blood rose by half, while other skeletal hormones barely budged.

In another test, just fifteen minutes after a few harmless ( but which were uncomfortable) shocks to their feet, osteocalcin protein levels in the stressed mice raised by a whole 150 percent.

Giving the test mice subjects a whiff of a chemical found in fox urine also elevated their peripheral osteocalcin protein levels. In addition to this, these went up before their corticosterone hormone levels began to climb, which started after a few minutes post the exposure and remaining high for another 3 hours.

Just to make sure it was not only a mouse thing, but the research team also checked the hormone in humans who volunteered to do a public speech and also undergo a pulse-raising cross-examination. Sure enough, up the osteocalcin went.

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In yet another series of tests conducted by the team, they used rodents that were genetically engineered to lack the usual corticosteroid hormone and other stress hormones and found these animals continued to present a stress response.

In addition to this, a shot of osteocalcin protein in otherwise unstressed mice was all they needed to get twitchy by raising their heart rate, the temperature of the body and levels of circulating glucose.

Karsenty further added that osteocalcin could explain past observations of an intact flight-or-flight response in humans and also in other animals lacking glucocorticoids and additional molecules produced by the adrenal glands. They discovered that the bones triggers fight-or-flight response, it is not the adrenaline!

With the evidence building for the bone osteocalcin protein as such a strong motivator for dealing with stresses, it stands to ask why we actually need hormones like cortisol at all. The scientists are planning to unravel this mystery in their future investigations.

This research was published in Cell Metabolism.


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Ria Roy completed her Post Grad degree at the Visvesvaraya Technological University. She has a great grounding in the skills, including technical, analytical and research skills. She is a motivated life science professional with experience of working in famous research institutes