A New Biochemical Link Established Between Stress, Sex And Dominance

In a study published Aug. 15 in the Journal of Neuroscience, a research team led by Stanford neurobiologist Russell Fernald has shown that continuous high levels of a stress hormone, cortisol, work to prevent most male cichlids from developing the bright, warlike colors, the extra muscles and the fully mature sex organs of a dominant "territorial" male.

Stress appears to prevent all but the dominant males from achieving reproductive success. Fernald said that since many species have evolved dominant and non-dominant males, the role of stress hormones in social systems may be widespread.

"The interesting new thing we have found is that stress depends not only on the social state of the individual male but also on the stability of the community," Fernald said.

Fernald is the Benjamin Scott Crocker Professor of Human Biology and director of the Human Biology program at Stanford. He is also a professor of psychology and a member of the Neurosciences program faculty. He and members of his laboratory already have shown that for cichlid fish, social position determines physiology. It's not so much that the biggest, brightest fish becomes dominant. Instead, a fish must earn his bright "macho" colors by proving to himself and others that he can control and defend a patch of food-laden gravel.

Those males that prove themselves ­ Fernald and his students call them "territorial" ­ experience a dramatic transformation, switching color within minutes from a camouflaged sandy gray to bright blue or yellow. Within days, they put on weight, mature sexually and sport a threatening, warpaint-like stripe next to their eyes.

As in the movies, the macho fish also gets the girl: He offers grazing rights to entice breeding females to lay their eggs in a sheltered nook within his territory. Only territorial males have the fully developed gonads capable of producing sperm to fertilize those eggs.

All in the head

All of this is reflected in a patch of cells in the fish's brain that increase eight-fold in volume while they pump out big doses of gonadotropin releasing hormone (GnRH), the coordinator of sexual development for all vertebrates, including humans. Most remarkably, if a territorial fish is defeated by another territorial male and loses his status, he loses the symbols of status as well. The colors and eyepatch fade, the GnRH cells in the brain shrink and so do the gonads.

"In our lab, we have shown that behavior influences the brain," said Fernald. "We've seen that behavioral encounters can modify the GnRH producing cells, and we know that this hormone in turn triggers changes in body structures that influence reproductive success. Now we want to know how social behavior can produce such changes in brain cells."

He and his students looked at cortisol as a possible mechanism. Cortisol is the "fight or flight" hormone, squirted out by the adrenal gland to give an animal a sudden burst of strength or speed so it can fight off an attacker or zip away from a predator. Other scientists have shown that cortisol levels remain high in the body if an animal ­ or a human ­ is constantly under stress. The hormone appears to be a trigger for many of the physiological effects linked to long-term stress, from sour stomach to heart disease.

Territorial rights

The Fernald lab is stacked with aquariums equipped to imitate the conditions of life in shallow pools of Lake Tanganyika, where this breed of cichlid fish originated. On the aquarium floor, a layer of gravel is piped with plastic tubing to deliver fish food from below ­ in the wild, cichlids sift through gravel to eat the decaying plant matter collected there. Overturned flower pots imitate the rocky nooks that male cichlids defend as spawning sites in their territories. By setting up various versions of this environment and introducing various combinations of male and female fish, Fernald has been able to study social behavior and the physiological and neurological changes that it entails.

The cortisol research was primarily conducted by three students. Helen E. Fox, a 1994 graduate of Swarthmore, worked in the Fernald lab for two years before starting graduate studies at the University of California-Berkeley. Stephanie A. White earned her Ph.D. in neurosciences at Stanford this year and is now a postdoctoral fellow at Duke University. Mimi H.F. Kao won a Firestone Medal for her cortisol research while earning her bachelor's degree in human biology at Stanford in 1995. Now she is working toward a graduate degree in neurosciences at the University of California-San Francisco.

They tested the hormonal response to stress by capturing the fish and taking blood samples before returning them to the tank. First, they determined that if a sample was taken within four minutes after capture, cortisol levels represented the baseline amount of hormone that was in the fish's bloodstream in the tank, not the big spurt pumped out by the adrenal gland during capture.

Fernald said that the team's major finding came from an experiment where 20 male and female fish were introduced to a large aquarium, with gravel and potsherds placed over half the floor and the other half left bare as a refuge from territorial wars. The fish were all new to one another; none had been raised in the same tanks. Most of the males were still sexually immature.

The males immediately began vying for patches of territory. For the first few weeks, ownership changed frequently ­ and so did the males' bright colors, switching on or off depending on which male perceived himself to be the victor. Perhaps most important, Fernald said, was the fact that no females elected to lay eggs during this period of social instability.

Eventually, several males established permanent territories and began their transformation into large, bright, dominant animals. The other males remained almost indistinguishable from females. That nondescript coloring has its advantages: A non-territorial male can sneak into a dominant male's territory by impersonating a female, and snatch extra food.

This behavior is the same as in Africa, where Fernald has done field work. And in the wild, a brightly colored fish is more likely to be snatched up by a wading bird. But Fernald's team knew from previous experiments that if males were raised alone, they would take on the flashy traits of a dominant fish. What happens in social situations to suppress some males' maturation?

The scientists found two kinds of evidence that cortisol is at least one of the factors mediating between behavior and physiology. Early in the period of social instability, both territorial and non-territorial males showed similar cortisol levels, with males that were territorial at the time of a blood test showing somewhat higher levels than non-territorial males. That is consistent with cortisol's known role as a fight-or-flight hormone, marshaling the resources needed for a battle.

Once the social system was stable, however, the territorial males' cortisol levels dropped dramatically ­ even though such fish are constantly active, chasing away other males and enticing females. Meanwhile, the stress hormones in the blood of non-dominant males skyrocketed once their competitors had control over all the available territory. Those cortisol levels stayed high for the remainder of the study.

The differences in cortisol levels between territorial and non-territorial males and between stable and non-stable social situations provide evidence that this stress hormone response tracks both the individual's social status and the dynamics of its social scene, the scientists concluded.

The hormone differences also offer tantalizing evidence that cortisol might be the mediator between the social situation and the non-territorial males' failure to mature. Continuous high levels of stress hormones might affect the size of GnRH producing brain cells, Fernald said ­ but this study does not offer positive proof of that hypothesis. More research, involving implants of cortisol and a cortisol antagonist in selected fish, may answer that question in the future.

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NOTE TO REPORTERS: The article "Stress and Dominance in a Social Fish" by Helen E. Fox, Stephanie A. White, Mimi H.F. Kao and Russell D. Fernald appears in the Aug. 15 issue of the Journal of Neuroscience. An abstract is available on the journal's website at http://www.jneurosci.org/.

A review article, "Changing Through Doing: Behavioral Influence on the Brain," by Stephanie A. White and Russell D. Fernald appears in the 1997 Endocrine Society publication, Recent Progress in Hormone Research, Vol. 52. Copies of both articles are available from the Stanford News Service, and from Russell Fernald.

By Janet Basu