Winter aggressiveness in male mice, due to estrogen

May 22, 2007 11:21 GMT  ·  By

Who says women are not aggressive?

Scientists were puzzled when they noticed that female hormone estrogen induces calm and relaxation during the long summer days and aggressiveness during short winter daylight in the male Oldfield Mouse (Peromyscus polionotus), a native to southeastern US. This is one of the first researches linking the length of daylight to gene-influenced behavior. "We found that estrogen has totally opposite effects on behavior in these mice depending only on how much light they got each day," said co-author Brian Trainor, postdoctoral fellow in psychology and neuroscience at Ohio State University. "While other studies have examined how environment interacts with genes to influence behavior, most of these studies have examined very complex environmental conditions," said co-author Randy Nelson, professor of psychology and neuroscience at Ohio State.

Male mice were castrated to get off testosterone production and given a drug which stoped the estrogen production (commonly employed in treating estrogen-dependent breast cancer). The drug made the mice less aggressive during the winter months. But when these mice were kept in summer long daylight, they behaved more aggressively.

Estrogen was indeed behind the aggressiveness levels in these mice.

In another test, the researchers checked which estrogen receptor (alpha or beta) was more important in inducing the mice' behavior. The team administered to one mice group an estrogen imitator that binds primarily to estrogen receptor alpha, while the other group received a drug akin to estrogen receptor beta: the results were identical (aggression in winter, calmness in summer). "The differences in how estrogen affected behavior in long days compared to short days could not be explained by the hormone using different receptors in different times of year," Trainor said.

Microarrays method showed that certain genes linked to estrogen were more active in the long-day mice than in the short-day mice. "That suggested that estrogen works in mice living in long days through these specific genes, creating a genomic pathway leading to less aggressive behaviors", Trainor said.

But estrogen appeared to increase the level of aggression in short-day mice through other cellular mechanisms than gene activation. When hormones are active through genomic pathways, behavioral effects emerge in hours, days or even weeks.

But when hormones eschew the gene-controlled mechanism, behavior can shift in just minutes.

Injecting estradiol (an estrogen type) in mice in winter-like short days boosted aggression almost immediately; however, its effects were not noticeable so soon on the mice living in longer day lengths. "In the vast majority of cases, hormones seem to affect behavior by working through genomic pathways, so it is always interesting when you find something different. This seems to be one of those instances where estrogen is working in a different way in long-day mice. But there is a lot more work to be done to understand this", said Nelson.

The researchers also reveal the importance of checking the estrogen role in human aggression. "In general, estrogen works to inhibit aggression in humans, but this study suggests research needs to look more at the role of estrogen receptors in some parts of the brain," Nelson said. "A lot of the research looks at how genes and hormones work in a controlled environment outside the body. But this study shows that the environment can play a very significant role in how estrogen reacts in mice," Trainor said.

"If something as simple as the length of day can affect how estrogen is used in the body, at least in some species, how are other environmental factors such as diet affecting estrogen in humans? It is something we don't know enough about." (as estrogen is linked to breast cancer). "This goes against the common belief that testosterone is the hormone that regulates aggression. There are now several studies showing that in some species estrogen plays a key role in aggressiveness as well", Nelson explained.