BioWorld International Correspondent
LONDON - The ability to control the fertility of domestic animals, develop new contraceptives or fertility drugs for humans - and even design perfumes that would act as sexual attractants or bring about desirable changes in mood - could follow from work on pheromone receptors in mice.
Scientists working in Switzerland have proved that pheromones stimulate a family of receptors found in most mammals, and have identified the first receptor-pheromone pair. The technique they used to make these discoveries will make it possible to identify many other receptor-pheromone pairs, including those thought to be present in humans.
Ivan Rodriguez, professor in the department of zoology and animal biology at the University of Geneva, told BioWorld International, "Our finding will make it possible to test different molecules and this will probably allow us to identify the signal transduction cascade involved and find ways to modulate it."
Rodriguez, who already has identified five similar receptors from the same family in humans, said one of the team's goals is to find ligands for the human receptors. They will, for example, test sweat, in which the molecule that is responsible for the synchronization of the menstrual cycle among women living together at close quarters is found. "Despite what some people selling products that are supposed to act as sexual attractants would have you believe," Rodriguez said, "no human pheromone has yet been identified."
The work is published online in a brief communication in the November 2000 issue of Nature Neuroscience and titled "Pheromone detection mediated by a V1r vomeronasal receptor."
Pheromones are molecules produced by animals and detected by others of the same species. The detection of a pheromone can trigger a change in behavior, such as displays of aggression, submission or sexual arousal, or can result in endocrine modification, such as triggering ovulation or speeding up sexual maturation.
Scientists had known for a long time that a small organ in the nasal cavity, called the vomeronasal organ, played an important part in communication between individual mammals. Seven years ago, researchers reported that the neurons present in this organ in rodents expressed a huge family of about 150 receptors. The sensory neurons of the vomeronasal organ project dendrites toward the outside, and the dendrites are covered with receptors, each neuron expressing just one of the 150 receptors.
"No one knew what the ligands for these receptors were," Rodriguez said. "A few years ago, we and others demonstrated that they played a role in axon guidance, but we still hoped that they had a direct role in pheromone recognition."
In collaboration with Marie-Christine Broillet of the University of Lausanne, also in Switzerland, and colleagues, Rodriguez set out to show that this was the case. They generated transgenic mice in which the gene for green fluorescent protein was added alongside that for one of the receptors. When the receptor was expressed, the neuron would turn fluorescent green.
This allowed the team to visualize those neurons expressing the receptor of interest. When they added a range of molecules, including some that were mouse pheromones, they were able to identify which molecules triggered a response in the labeled neurons.
"We were able to show," Rodriguez said, "that the neurons expressing the receptor V1rb2 responded to the mouse pheromone 2-heptanone. Our next step was to demonstrate that the receptor itself provided the capacity for the neurons to respond. So we used another mouse, which again expressed green fluorescent protein alongside the gene for the receptor, but in this case the receptor gene was mutated so that the receptor itself could not be made. When we added the pheromone, we found that these neurons did not respond, proving that the receptor itself provides the sensitivity to the pheromone."
The finding, together with the method used for the discovery, could have important applications. Rodriguez explained that pheromone reception is crucial to mammalian species. "This ability is necessary for survival. An animal that cannot detect pheromones will not itself die as a result, but the next generation will never be born. We are now beginning to understand how this system works at the molecular biological level. We have the molecular tools and we can design many novel experiments."
Further scientific work on pheromones and their receptors could lead to new ways of modulating the fertility of cows and pigs and other animals bred for consumption, he said. New fertility drugs or contraceptives also could result. Ways of modifying human behavior or feelings would also, he predicted, be of interest to the perfume industry.
Although humans have a vomeronasal organ during embryogenesis, Rodriguez believes that it disappears and is not functional in adults, even though a small pit remains in the nose at its location. "Scientists are not in total agreement about this, but I don't believe that we perceive pheromones through this organ," he said. "But many mammals perceive pheromones via the main olfactory system, and that is where one of the human receptors is found."