Dr. David Anderson

and it gets input from about 30 different regions.

So I kind of see it as both an antenna and a broadcasting center.

It's like a satellite dish that takes in information from different sensory modalities, smell, maybe vision, mechanical sensation, and then it sort of synthesizes and integrates that

into a fairly low dimensional, as the computational people call it, representation of this pressure to attack.

And it broadcasts that all over the brain to trigger all these systems that have to be brought into play if the animal is gonna engage in aggression.

because aggression is a very risky thing for an animal to engage in.

It could wind up losing and it could wind up getting killed.

And so its brain constantly has to make a cost benefit analysis of whether to continue on that path or to back off.

When we finally identified the neurons in VMH that control aggression with a molecular marker, we found out that that marker was the estrogen receptor.

Other labs have shown that the estrogen receptor in adult male mice is necessary for aggression.

If you knock out the gene in VMH, they don't fight.

And it's been shown, and a lot of this is work from your colleague Nirav Shah at Stanford, who is one of my former PhD students, that if you castrate a mouse and it loses the ability to fight, not only can you rescue fighting

with a testosterone implant, but you can rescue it with an estrogen implant.

So you can bypass completely the requirement for testosterone to restore aggressiveness to the mice.

And as you say, it's because many of the effects of testosterone

although not all, many of them are mediated by its conversion to estrogen by a process called aromatization.

It's carried out by an enzyme called aromatase.

In fact, people may have, most of your listeners may have heard of aromatase because aromatase inhibitors are widely used in female humans as adjuvant chemotherapy for breast cancer.

So we and other labs have studied this in both mice and also in fruit flies.

One thing in mice that distinguishes aggression in females from males is that male mice are pretty much ready to fight at the drop of a hat.