Candidate Receptor Turns on Human Pheremone Debate

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Lancet, 09/02/2000, Vol. 356 Issue 9232, p835, 1/2p
SCIENCE AND MEDICINE
CANDIDATE

RECEPTOR TURNS ON HUMAN PHEROMONE DEBATE
Pheromones are considered important for intraspecies communication in many

mammals, though the anatomical and molecular substrates are not fully understood. Scientists have now identified a

candidate human pheromone receptor, a finding that promises to further debate over the importance of pheromones in

human behaviour.
Rodents possess a specialised pheromone-detection structure, the vomeronasal organ (VNO),

alongside the main olfactory epithelium. Timothy Holy (Harvard University, MA, USA) and co-workers report this week

that the responses of individual mouse VNO neurons to putative pheromones differ from activity in sensory neurons

(Science 2000; 289: 1569-72). Further, the authors suggest that the heterogeneity observed in VNO responses is

"consistent with the existence of over 100 different putative receptor genes", coded by the V1r and V2r gene

families.
The story in human beings is less clear. Some groups suggest that pheromones can modulate some human

behaviours and physiology, such as synchronisation of menstruation between cohabiting women. Ivan Rodriguez and a

team led by Peter Mombaerts (Rockefeller University, NY, USA) have now used a genomic approach to investigate human

homologues of putative rodent pheromone receptors. After a genome-wide search, the team identified eight human V1r

homologues. One gene, V1RL1, had an uninterrupted open reading frame in 11 ethnically diverse individuals,

suggesting it is an active gene throughout the population. V1RL1 mRNA was reliably detected only in human olfactory

mucosa (Nat Genet 2000; 26: 18-19).
Michael Meredith (Florida State University, FL, USA) is cautious about whether

V1RL1 can be considered a candidate human pheromone receptor on the basis of homology with VNO receptors because the

VNO "may not be exclusively concerned with pheromones". The next step would be to determine "if [V1R1] is expressed

in any VNO cells and, if so, whether those cells have any neural connection with the brain". Finding the cell type

is "not a trivial task", counter Mombaerts' team. And says Mombaerts, "We have shown that V1R1 is expressed in the

main olfactory mucosa. This fulfills an important minimum criterion for an involvement in chemosensation." Both

agree that the debate over the existence of a human correlate of the rodent VNO may be a red herring, because in

many species, the main olfactory epithelium is thought additionally or exclusively involved in mediating pheromonal

effects.
Biotechnology company Senomyx (San Diego, CA, USA) will now search for ligands that activate or block

V1RL1, says Mombaerts. If the gene product is found to act as a pheromone receptor, such ligands might have future

applications for premenstrual syndrome, sexual problems, and even increasing self-confidence, he speculates.

Meredith is less sure: "I think it is likely that there are human pheromones . . . but we should not expect them to

have more than a minor effect on behaviour".
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By Kelly Morris

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