Pituitary vasopressin signaling realigns the body clock for recovery from jet lag: study

Jet lag is a head issue. What exactly is late has more to do with the hypothalamus than the jet.

A misalignment of the body’s internal clock following air travel across multiple time zones leads to lack of sleep and physical discomfort. The master clock in the tiny suprachiasmatic nucleus – or SCN in the anterior part of the hypothalamus – keeps the departure time and requires several days to adjust to the destination time.

While the exact cause of jet lag remains a mystery, a team of researchers from Kyoto University and Kansai University revealed that essential vasopressin signaling in the neuroendocrine circuits of the hypothalamus and anterior pituitary gland could provide clues to its role in the pacemaker of the SCN. The work was published in the Proceedings of the National Academy of Sciences.

“The role of rhythm generation by the extra-SCN anterior pituitary-neuroendocrine system might have gone unnoticed without the advent of intercontinental air travel in the 1950s, which provoked an artificial and uniquely human experience,” explains the researcher Hitoshi Okamura. from KyotoU Graduate School of Medicine.

Subsequent studies found that SCN lesions suppressed all circadian rhythms in the body and that isolated SCNs could generate robust circadian rhythms. This discovery led researchers to believe that only the neural circuits of the SCN clockwork mechanism can adjust the time difference to new light-dark cycles.

Previous research showed that global inhibition of vasopressin V1a and V1b receptor signaling eliminated jet lag. Okamura’s team is currently trying to identify the critical sites of these receptor systems. So far, researchers have determined that vasopressin and its receptor V1b in the anterior hypothalamic-pituitary systems can help maintain original time during jet lag.

To date, there are no effective medications for the syndrome, mainly because current medications only target the SCN. The revelation that the hypothalamic-pituitary systems orchestrate a synchronized response to the body’s disrupted circadian rhythm has inspired the development of more effective treatments.

“The development of vasopressin inhibitors on multiple targets – not only V1a in the SCN but also V1b in the pituitary – could significantly contribute to alleviating jet lag,” says Yoshiaki Yamaguchi of the Faculty of Chemistry, Materials and in Bioengineering from Kansai University.

“Addressing the different parts of the neuroendocrine system that collectively work on the cellular clock in the SCN is an important step toward a deeper understanding of how our biological clocks maintain time even during rapid fluctuations in light,” explains Okamura.