To ensure all living animals and humans avoid as much danger as possible, they have an inbuilt ‘fight-or-flight’ response. The fight-or-flight response, also known as the acute stress response (ASR), is a physiological reaction mediated by the sympathetic nervous system. Indeed, this reaction plays a critical role in helping animals react to potentially life-threatening situations.

More specifically the adrenal glands, which sit on top of the kidneys, release a variety of hormones such as adrenaline, norepinephrine, and cortisol which in turn triggers a physiological response. Meanwhile, as these glucocorticoid hormones require hours to alter physiological responses, there appears to be a gap in the theory of an immediate response to danger.

Bone controls fight or flight

Now, researchers at Columbia University show in bony vertebrates the ASR is not possible without osteocalcin, a hormone produced by bone. The team states that almost immediately after the brain recognizes the danger in mice and humans, it instructs the skeleton to flood the bloodstream with osteocalcin. Hence, this is the chemical that is needed to turn on the fight or flight response. The opensource study is published in the journal Cell Metabolism.

Previous studies show the bones which make up the skeleton secrete a protein called osteocalcin which rebuilds the skeleton. Recent studies from the group showed this protein acts as a hormone to keep blood sugar levels in check and burn fat. Later, the lab showed osteocalcin is important for maintaining brain function and physical fitness, restoring memory in aged mice, and boosting performance during exercise in old mice and people.

The findings led the researchers to hypothesize animals evolved bony skeletons to memorize and escape danger. The current study shows both rodents and humans release a bone-derived hormone called osteocalcin in response to acute stress.

The current study exposes mice to several stressors, including a mild electric shock to the foot and a whiff of fox urine, and then measures the levels of osteocalcin in the animals’ blood. Results show within 2 to 3 minutes of being exposed to a stressor, levels of osteocalcin in the mice quadrupled. Data findings show when participants were asked to speak in front of an audience, osteocalcin levels also spiked.

Bone hormone before adrenaline

Results show when osteocalcin levels increased, heart rate, body temperature, and blood glucose levels in mice also rose as the fight or flight response kicked in. Data findings show, in contrast, mice genetically engineered so they are unable to make osteocalcin or its receptor are indifferent to the stressor, with ASR induced simply by injecting osteocalcin.

The team surmises their findings suggest osteocalcin, not adrenaline, is the gatekeeper which determines when the body shifts into fight-or-flight mode. For the future, the researchers state their study raises the question of why cortisol rises during the ASR, and now plan to expand their studies to primates to help define the neuronal road map from the brain to the bone in more detailed ways.

Source: Columbia University Irving Medical Center 

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