Crucial breakthrough in sex-specific behavior

21 August, 2007:

In a very interesting and significant breakthrough, researchers have found that the huge difference between male and female sexual behavior may be
explained, in animals at least, by a tiny organ in the nose rather than by any gender difference in brain circuitry.

Earlier work has suggested that hormones like testosterone might create this difference during development.

Investigators at Harvard University, the United States, say they were stunned by the finding and the implications for the understanding of sexuality.

In a study published in the British journal Nature on August 5, 2007, the team says that they engineered female laboratory mice so that the rodents
lacked a gene called TRPC2, effectively short-circuiting the so-called vomernasal organ.

However, the results do not apply directly to humans because of the absence of the vomeronasal organ.

Yet, the study may offer pathways to understand sex-specific human behavior.

This tiny organ in the nose is packed with receptor cells that pick up pheromones – primitive scents that trigger aggression and sexual response in land-dwelling vertebrates.

To the utter surprise of the researchers, the mutant female mice behaved like men at a ‘disco night.’ The mutant female mice sniffed and ran after females, flounced their pelvises, mounted and thrust at male mice, issuing ultrasonic squeaks of the kind that males emit to show love.

However, the behavior was not all-male. The genetically engineered female mice mated with males in a manner typical of the female, and, unlike normal males, they did not attack other males.

But, when their babies were born, they again became irresponsible males, unconcerned about raising their offspring and keen on having more sex.

Usually, female mice spend around 80% of their time in their nest nursing their newborns and while lactating will attack male intruders and reject any
attempt at a cuddle.

The new findings suggest that a normal female mouse has the capability to carry out both female and male behaviors throughout her life. However, when the female mouse encounters a simple signal, like a pheromone, she shuts off the male behavior and turns on female behavior.

The bottomline could be that interpretation of sensory cues, rather than the effect of hormones on brain structure, may be responsible for the behavioral difference between the two genders in mice.

While this study looks at the effect of pheromones on behavior, it does not suggest a specific mechanism for how processing the sensory information
leads to a change in behavior.

According to Catherine Dulac, professor of Molecular and Cellular Biology in Harvard’s Faculty of Arts and Sciences and an investigator with the Howard Hughes Medical Institute, there are two possible interpretations: either the vomeronasal organ may be needed to grow a female-specific neural circuit during development, or the mature female mouse brain may require vomeronasal activity to repress male behavior.

To test the alternatives, Dulac and her colleagues cut out the vomeronasal organs from the nasal septa of normal adult females. These mice began exhibiting male behaviors, though they showed testosterone levels, oestrogen levels, and oestrus cycles indistinguishable that is found in normal females.

Dulac and colleagues are now trying to understand the behavior of male mice mutant for TRPC2 to see if they display female-like characteristics.