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When humans and animals are faced with danger, hormones (glucocorticoids) flood the body in preparation for ‘flight or fight’, this is referred to as the acute stress response (ASR).  Consequently, physiological changes occur in the body, for example the heart and breathing rate increases.  The production of glucocorticoids is regulated by the hypothalamic–pituitary–adrenal (HPA) axis in mammals and birds.  Up until recently it was considered that hormones linked to the HPA axis, such as adrenaline and cortisol, acted as messengers that triggered the flight or fight response.  However, a study by Meyer Berger et al. (2019) has highlighted that a protein in the body’s bones, called osteocalcin, may also play a key role.

The researchers undertook several tests involving mice, rats and humans.  These included: restraining mice and rats for a brief period, issuing low level electric shocks to the feet of mice, and exposing mice to the scent of a compound found in fox urine (data shows this triggers a rapid, hard-wired fear reaction in mice).  Additionally, human subjects were tasked with a public speaking exercise and a cross-examination style interview, both designed to trigger stress that increases heart rate and blood pressure. 

In every test – regardless of whether it was mice, rats or humans involved – osteocalcin rose, and in some instances the levels of this calcium binding protein rose quicker than corticosterone levels.  In fact, the experimenters found osteocalcin was even triggered in mice that had been genetically engineered to lack typical stress hormones linked to the ASR.  As a result, the researchers suggest these findings may explain why animals lacking glucocorticoid and other molecules produced by the adrenal glands, can still exhibit an intact ASR when faced with danger. 

When you think of it, this new information linking bone to stress responses makes sense.  It is the skeleton that protects our vital organs and helps us escape from harm.  As Gerard Karsent, one of the authors of this study, states: “Even the bones in the ear alerts us to approaching danger.”  

Such research opens debate, as the vast majority of glucocorticoid activity in mammals is from cortisol and virtually any type of physical or mental stress results in elevation of cortisol concentrations.  Thus, further investigation is required to understand why this and other hormones are even needed, if bone protein helps humans and animals deal with stress.    

Bowen, R. (2019) Colorado State University.
Meyer Berger, J., Singh, Khrimian, L., Morgan, D.A., Chowdhury, S., Arteaga-Solis, E., Horvath, T.L., Domingos, A., Marsland, A.L., Kumal Yadav, V., Rahmouni, Y., Kamal Y., Gao, X.,  R., and Karsenty, G. (2019) ‘Mediation of the Acute Stress Response by the Skeleton.’ Cell Metabolism. 

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