A Hormone Can Blind Female Mice to the Smell of Males

July 2015

Everyone knows that a plate of food doesn't look as delicious after you've already eaten a big meal. But imagine if your internal state actually made you blind to food.

Associate Professor Lisa Stowers (right) with Research Associate Sandeepa Dey.

In a new study, TSRI scientists found that when female mice are in are in diestrus, a period of sexual inactivity during the reproductive cycle, receptors in their nose cause an odor "blindness" by blocking the pheromone signals from male mice and preventing them from ever reaching the females' brains. The results may enable a better understanding of how pheromones work, possibly even in humans.

"This was shocking," said Lisa Stowers, associate professor and member of the Dorris Neuroscience Center at TSRI and leader of the new study. "The nose was making decisions and acting like an extension of the brain."

The new study started with a well-known observation in the field: While female mice are attracted to male mice during estrus – when they are receptive to breeding – female mice are indifferent to, and even aggressive toward, male mice during diestrus.

Researchers have long suspected that this is related to hormonal changes in the brain during the reproductive cycle. Hormones produced in the ovaries during estrus and diestrus are known to activate specific neurons in the female brain. Dr. Stowers and her team aimed to study those neurons further. Before they investigated the brain, however, they first wanted to rule out any activity in the nose that might be affecting the odor cues.

The researchers investigated a subset of neurons in a special organ in the nose called the vomeronasal organ (VNO), which detects male odors.

They discovered that these neurons have a "gating" mechanism and fail to activate in the presence of a hormone called progesterone, which is produced in the ovaries during diestrus. Without these neurons activating, the female's brain can't perceive male odors. Basically, the nose is acting independently of the brain.

"I have never heard of anything like this before – in any sensory system," said Dr. Stowers.

Next, the researchers wanted to see if progesterone was disabling VNO function altogether. To test this, they checked the VNO response to predator cues – in this case, the scent of cat urine, which mice instinctually avoid. The researchers found that the subset of VNO neurons that usually respond to cat urine continued to respond normally, even in the presence of progesterone.

This showed that the ability of female mice to smell in general was indeed still active during periods of diestrus.

The researchers then took a closer look at the signaling process. They discovered that when progesterone is detected by VNO neurons, a signaling molecule that would normally relay the odor to the brain changes. Because only male odor-specific VNO neurons are susceptible to this change, they are the only ones that switch off in the presence of progesterone.

The reason for this male odor "blindness" is still unclear. Dr. Stowers said there is no evidence for the notion that male odors distract females from finding food or shelter. After all, female mice can smell male mice during estrus, and they still survive.

"In the wild, there has to be some reason the female isn't detecting those cues," said Dr. Stowers.

Future studies in Dr. Stowers' lab will focus on whether neurons in other areas of mouse noses – and human noses – are affected by hormone fluctuations and other internal-state changes, such as appetite and stress.

"We think this is just the tip of the iceberg," said Dr. Stowers.

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