Juvenile sea lampreys attached to aquarium wall by suction. Photo credit: Stephen McCormick.

Juvenile sea lampreys attached to aquarium wall by suction. Photo credit: Stephen McCormick.

Give many creatures a nasty shock and a physiological chain of events kicks into action. The victim's body floods with specialised stress hormones, known as corticosteroids, that in turn inundates their blood with glucose for energy, ready to take on any threat. ‘This mobilization … in response to stress is a fundamental and classically described component of a ‘fight or flight’ response to stress in vertebrates’, says Ciaran Shaughnessy from the University of Massachusetts, Amherst, USA. But no one knew just how far back this fundamental protection mechanism went. Mammals and many fish tend to depend on a selection of corticosteroids when they prepare to fight for survival, while amphibians, reptiles and birds usually rely on one: corticosterone. But then things get a bit hazy. Most ancient creatures use simpler corticosteroids, which are essentially the building blocks of the more complex corticosteroids that fish and mammals depend upon today. Knowing that lampreys are the oldest surviving ancestor of almost every terrestrial and aquatic animal alive today, Shaughnessy and Stephen McCormick (University of Massachusetts, Amherst) wondered whether these living fossils also use corticosteroids to help when they need to get out of a tight corner.

‘The production of corticosteroids in lamprey and hagfish appears to be incomplete compared to that of more modern, back-boned animals’, says Shaughnessy, explaining that these ancient ancestors produce the relatively simple corticosteroid 11-deoxycortisol. Then, the duo began to check whether this cut-down stress hormone could trigger the release of glucose in the animals’ blood when they encounter a challenge.

After collecting lamprey (Petromyzon marinus) larvae and juveniles from the nearby Connecticut River, the duo delivered the parasitic fish to their new home in the Conte Anadromous Fish Research Laboratory. There, they briefly held the fish in a net before dropping their water level for 10 min to get them wound up. ‘This modest physical disturbance was enough to get the animal to mount a robust physiological stress response’, Shaughnessy says. Then, he measured the amount of 11-deoxycortisol in the lampreys’ blood and discovered that the larvae's corticosteroid levels had rocketed from 2 ng ml−1 to 16.7 ng ml−1, an increase of more than 8 times, while the juveniles’ response was less dramatic, but almost quadrupled from 1.7 ng ml−1 to 6.4 ng ml−1. In addition, both life stages experienced a blood glucose surge. And, when the researchers checked the animal's bodies for evidence of the enzymes that produce 11-deoxycortisol, they turned up in the animal's kidney, while the enzymes that produce glucose were mostly located in the liver. So, the stressed lampreys were able to produce a ‘fight or flight’ hormone and release glucose from the liver into their blood, but was the hormone actually responsible for the lifesaving glucose gush?

To check this, Shaughnessy injected increasing doses of 11-deoxycortisol into lampreys and, sure enough, their blood glucose levels rocketed. Also, the hormone triggered expression of one of the key enzymes that contributes to glucose production in the animal's liver – phosphoenolpyruvate carboxykinase.

In short, lampreys depend on a corticosteroid for their fight or flight response just like their modern descendants, suggesting that almost all vertebrates inherited this ability almost 500 million years ago from these ancient ancestors. ‘It amazes me that all of these vertebrate physiological systems were present and swimming around in the ocean before land plants even existed on Earth’, says Shaughnessy, who is now hoping to find out how these prehistoric creatures control production of their powerful stress hormone to understand how fear has helped animals to survive on our planet over hundreds of millions of years.

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11-Deoxycortisol is a stress responsive and gluconeogenic hormone in a jawless vertebrate, the sea lamprey (Petromyzon marinus)
J. Exp. Biol.