Estrogen, The Female Sex Hormone, May Influence Aggression In Both Men And Women

Researchers show how estrogen-producing nerve cells exert specific effects on aggressive behavior in both male and female mice. Pier-Luc Bergeron

Generally, we think of estrogen as a female sex hormone, but during the 1970s it was discovered that testosterone, the male sex hormone, can be converted in the brain into estrogen. Now, a new study suggests estrogen may serve an important function in the brain, one that even encourages violence… at least, in mice. Estrogen-producing nerve cells, UC San Francisco researchers discovered, exert specific effects on aggressive behavior in both male and female mice.

“Though social behaviors — marking of territory, recognizing potential mates, successfully mating, fighting — seem quite ‘seamless’ when we observe them, this study shows that different neural systems control quite distinct, specific components of these behaviors,” Dr. Nirao Shah, senior author of the study, stated in a press release.

Working with adult mice, Shah and a team of researchers depleted estrogen-producing nerve cells — also known as aromatase-expressing (aromatase+) cells — in a brain region known as the posterodorsal medial amygdala, or MeApd. This structure, in which aromatase+ cells make up 40 percent of the total neurons, is vital to social and reproductive behavior. In fact, it is linked to the olfactory bulb in the forebrain where it receives smell and pheromonal information commonly used by mice to identify other mice and to respond appropriately.

Using a genetic technique, the researchers eliminated the small cluster of aromatase+ cells from the MeApd in males, then in females. At first, the genetically modified male mice behaved as they normally do: They marked their territory, and they recognized, courted, and successfully mated with females. However, when these mice encountered an unfamiliar male in their territory, they showed a dramatically altered social style.

Typically, male mice rattle their tails and then attack a same-sex intruder. The mice without aromatase+ neurons, though, showed less tail-rattling, and then it took them longer to mount an attack. In fact, the researchers saw a direct relation between the number of aromatase+ cells that had been eliminated and the lag time before an attack. Strangely, when these genetically modified mice finally did attack, the aggressiveness of their fighting resembled that of normal males.

In females, the consequences of depleted aromatase+ cells only played out after they’d given birth. The genetically modified females responded to male mice in all the usual ways, but then, strangely, they seemed to lack the normal level of maternal aggression. Generally, female mice with nursing pups will attack unfamiliar male mice, which are known to kill rival males' pups.

However, these genetically modified females were slow to attack while nursing. Like the genetically modified males, though, they became indistinguishable from normal female mice once the fighting commenced.

"In theory, these estrogen-producing neurons could have controlled any part of social behavior, or all social behaviors, but we found they control only a very small component of aggression," said Elizabeth K. Unger, a graduate student in the Shah lab and first author of the study. "And considering females do not need these cells to produce estrogen, it was quite surprising to find that these cells play a similar role in both males and females."

Source: Unger EK, Burke KJ, Yang CF, et al. Medial Amygdalar Aromatase Neurons Regulate Aggression in Both Sexes. Cell Reports. 2015.

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