Researchers identify molecule
that may be key in pheromone processing
Result suggests different mechanisms for rodents and humans

BOSTON – May 3, 1999 – A research team at the Massachusetts General Hospital (MGH) and Harvard University has identified a molecule that may be key to the process by which the chemical signals called pheromones are turned into nerve impulses travelling to the brain in rodents. The discovery, which appears in the May 11 issue of Proceedings of the National Academy of Science, has two unusual aspects: the molecule is most similar to one that insects use to receive visual signals, and it is produced by a gene that is defective in humans.

"This finding doesn’t mean that we all should throw out our expensive perfumes and colognes," says first author Emily Liman, PhD, of the HHMI at MGH. "Instead it suggests that humans probably process pheromones through a different mechanism than most other mammals do." The research team also includes David Corey, PhD, MGH; and Catharine Dulac, PhD, of Harvard University. All team members also are researchers with the Howard Hughes Medical Institute.

Many aspects of animal behavior – particularly those relating to courtship and mating – are known to be controlled by pheromones. Although they are detected via the nose, most pheromones are received by a structure within the nose called the vomeronasal organ (VNO), whereas odors are received by the main olfactory epithelium (MOE). While pheromones are believed to play a role in the timing of women’s menstrual cycles, any larger role in human physiology is poorly understood.

Earlier research by Liman, Corey and others has shown that the molecular pathways by which odors are detected in the MOE are not active in the VNO. Similarly, pheromone receptors (molecules on the membrane of a cell that initially receive a chemical signal) recently identified by Dulac are not chemically related to the odor receptors found in the MOE. With this evidence of different mechanisms for the detection of odors and pheromones, interest in discovering how pheromones transmit their signals has been intense.

The MGH/Harvard team has identified a molecule called TRP2 as a candidate for the ion channel involved in pheromone signalling in rats. Ion channels are tiny passageways into the cell that open in response to the activation of a receptor. When they open, ion channels admit charged particles into the cells, altering the cells’ electrochemical makeup. In nerve cells like those in the VNO and MOE, opening of an ion channel is key to transforming a chemical signal into a nerve impulse. In their analysis of VNO and MOE tissues from rats, the researchers found that TRP2 is present only in the VNO and only in the area where pheromones are known to be detected.

"Remarkably," says Liman, "TRP2 is not similar to the ion channel mammals use to detect odorants. Instead it is similar to one that fruit flies use to detect light. Therefore the sensory modality – whether chemicals or light waves are to be detected – doesn’t seem to matter in the evolution of sensory receptor neurons and their signalling pathways."

In addition, the authors note, the human form of the gene coding for TRP2 has been mutated and now produces a protein that is nonfunctional. This supports evidence based on anatomy suggesting that the VNO does not serve a purpose in humans and that research into how humans detect and process pheromone signals probably should concentrate on the cells of the MOE.

The research was supported by grants from the Howard Hughes Medical Institute and the National Institute on Deafness and Other Communication Disorders.

The Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $200 million and major research centers in AIDS, the neurosciences, cardiovascular research, cancer, cutaneous biology, transplantation biology and photomedicine. In 1994, the MGH joined with Brigham and Women’s Hospital to form Partners HealthCare System, an integrated health care delivery system comprising the two academic medical centers, specialty and community hospitals, a network of physician groups and nonacute and home health services.

Contact: Susan McGreevey, MGH Public Affairs

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