Steroids in female mouse urine light up nose nerves of male mice

A group of steroids found in female mouse urine goes straight to the male mouse’s head, according to School of Medicine researchers. They found the compounds activate nerve cells in the male mouse’s nose with unprecedented effectiveness.

Timothy Holy

“These particular steroids, known as glucocorticoids (GCCs), are involved in energy metabolism, stress and immune function,” said senior author Timothy E. Holy, Ph.D., assistant professor of anatomy and neurobiology. “They control many important aspects of the mouse’s physiology and theoretically could give any mouse that sniffs them a detailed insider’s view of the health of the animal they came from.”

Holy plans further research to see if activating the nerves in the male mouse’s nose leads to particular behavioral responses. He probes the male mouse’s reaction to chemical signals from female mice to advance understanding of pattern recognition and learning in the much more complex human brain. In 2005, he found that female mice or their odors cause male mice to sing.

Science has long recognized that urine, sweat and other bodily fluids contain chemical communication signals called pheromones that can influence the biology or behavior of others. Most mammals use the information in these signals for social purposes, such as establishing territory or dominance or in courtship and mating. In many cases, though, the specific chemical identities of the signals are unknown.

The study, published in the June 18 issue of The Journal of Neuroscience and led by recent graduate Francesco Nodari, identified compounds that are unusually potent stimulators of the mouse nose. The pheromones activate nerve cells 30 times as often as all the other pheromones previously identified in female mouse urine combined. In addition, several of the new signals activate specific nerve cells. This may mean the male mouse’s brain can assess different aspects of female mouse health by selectively analyzing individual pheromones.

The GCC pheromones that Nodari identified were sulfated, which means they had a chemical attachment comprising sulfur and oxygen atoms. This attachment is added to deactivate the steroids prior to excretion in the urine. When Nodari used an enzyme to remove these attachments, the GCCs lost their ability to activate nerves, further suggesting that the link between the sulfated GCCs and the nerve cells is a channel fine-tuned by evolution to carry information from female mice to male mice.

The nerves researchers studied in the male mouse nose are located in an area known as the accessory olfactory system. The system sends its outputs to a different part of the brain than the main olfactory system and is dedicated to detecting airborne particles. But researchers believe the accessory olfactory system focuses on compounds from sources that are physically very close to or touching the animal.

Holy said this focus on scents from nearby sources makes the accessory olfactory system “halfway between a taste system and a sense of smell.” He said the GCC pheromones account for approximately 75 percent of the signals detected in female urine by the male accessory olfactory system.