When we first presented these findings, endocrine experts were surprised by the potential implications for the treatment of metabolic diseases, chief among them being type 2 diabetes.
rodents and people. In mice, our work has shown that no other substance can compensate for a lack of osteocalcin when it comes to these functions. Is the same true for humans? We now recognize that the body is far more networked and interconnected than most people think. No organ is an island. The skeleton often seems to play a surprising role. If insulin impacts bone, bone should help regulate insulin. If testosterone has an influence on bone mass, the skeleton should act on the testes. And, most fundamentally, just as the brain talks to the skeleton, bone should help regulate the brain. We continue the search to learn how this bidirectional influence works. Danger Lurks While identifying multiple functions for a novel hormone is a good start, it raises a new question: the common link between them. Why does osteocalcin regulate these particular physiological functions? And what others might it regulate? One common link involves the prototypical human reaction to acute danger: the stress or “fight or flight”
osteocalcin from the mother’s bones crossed the placenta and helped shape the fetal brain: i.e., bones talk to neurons even before birth. Human Health Implications With age, bone mass decreases and memory loss, anxiety, and depression become more common. These may be separate, unfortunate facts about getting old, but they could also be related. Many physicians recommend exercise as a way to prevent age- related memory loss. Does it help, at least partly, by maintaining bones, which make osteocalcin, which in turn helps preserve memory and mood? In
my view, a higher bone mass means a greater capacity for osteocalcin production. A question before us is: Would it ever be possible to protect memory or treat age-related cognitive decline with a skeletal hormone? My vision of the skeleton as central to energy usage, reproduction, and memory has persuasive evidence in mice, but the extent to which these results translate to people remains an open question. Most hormones have similar functions in mice and humans. Still, osteocalcin is clearly not the only substance that regulates blood sugar, male fertility, and cognition, and its relative importance may be different in
response, a suite of physiological processes that were studied and
An endocrine mediation of the ASR
24 DANA FOUNDATION CEREBRUM | Summer 2020
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