Progesterone Regulates Male Mouse Behavior

February 27, 2003

Progesterone Regulates Male Mouse Behavior

EVANSTON— In an unexpected discovery, a team led by Northwestern University scientists has become the first to show that progesterone, a hormone usually associated with female reproduction and maternal behavior, plays a key role in regulating male aggression toward infants in mice. Testosterone, not progesterone, had been thought to be responsible.

The researchers found that the absence of progesterone’s actions reduced aggression while promoting positive paternal behavior. The findings, to be published online by the Proceedings of the National Academy of Sciences during the week of Feb. 24, suggest a new approach to studying an area of biology that has been poorly understood.

“We discovered that the hormone progesterone and its receptor are important in males, not just females,” said Jon E. Levine, professor of neurobiology and physiology, who led the provocative study. “Paternal behavior may be based in the same biology as maternal behavior.”

Like adult males of many other species, male mice rarely contribute to parental care and often attack or kill infants soon after birth. Although this hostile behavior had previously been attributed to testosterone, a correlation between testosterone and male behaviors directed at young has never been established. Seeking another explanation for the male behavior, Levine’s research team tested paternal behavior in progesterone receptor knockout mice. (These mice lack the gene that encodes progesterone receptors and thus the animals are not affected by the presence of progesterone.)

“In male knockout mice we noticed something quite startling,” said Levine. “They behaved differently, and the most obvious changes were a complete lack of aggression toward infants and the emergence of active paternal care. These animals are terrific dads.”

After breeding males of both the knockout and a control strain, the researchers found a complete absence of infanticide in the resulting litters born to knockout mice. Comparatively, 74 percent of the control mice committed infanticide. Additionally, knockout mice contributed significantly more paternal care than the controls by frequently contacting pups and retrieving them to nests.

In a separate experiment, the researchers used a drug to block the progesterone receptors in normal mice and found that these mice behaved like the knockout mice—they were highly paternal.

Because, like the controls, the knockouts exhibited similar levels of aggression toward other adult males, the researchers surmised that the knockouts’ general level of aggression, a testosterone-dependent behavior, is not affected in these animals. These results suggest that progesterone, and not testosterone, may be key in specifically controlling infant-directed aggression in male mice.

“The same neuroendocrine mechanism may be important in other mammals, including humans, but further research is required,” said Levine. “At least in the case of mice, this appears to be an important neurochemical switch that can increase paternal behavior and decrease aggressive behavior toward infants.”

Other authors on the paper are Johanna S. Schneider (lead author), Marielle K. Stone and Teresa H. Horton, from Northwestern University; Katherine E. Wynne-Edwards, from Queens University, Kingston, Ontario; and John Lydon and Bert O’Malley, from Baylor College of Medicine, Houston.

The research was supported by the National Institute of Child Health and Human Development.