Our long-standing interest in the study of pheromones underwent a renaissance five years ago, after the cloning of their putative family of receptors. Since this breakthrough, our understanding of the molecular logic of this sensory system has continued to grow, and two reports published last month are the latest important advances in the field. In the first report, which appeared in the September 1 issue of Science, Holy et al. have begun to unravel the neural code used by the neurons of the vomeronasal organ (VNO). In the second, published in the September issue of Nature Genetics, Rodriguez et al. have identified what seems to be the first human pheromone receptor.

Holy and his colleagues at Harvard took on the technically demanding challenge of recording simultaneously from numerous mouse VNO neurons and tested their responses to a well known source of pheromones — mouse urine. They observed that, in contrast to most cells in other sensory systems, VNO neurons did not adapt to the continuous presence of the stimulus. More importantly, they found that only a small fraction of cells responded equally well to urine from either sex, as most of them showed preference for either male or female urine. Moreover, another class of VNO neurons could even distinguish between the urine of two animals of the same sex, a finding that, according to the authors, could be related to the recognition of individual differences. Although these are the first steps towards deciphering the neural code of the VNO, they already point to profound questions. How are these differences in firing pattern interpreted by the accessory olfactory bulb? Do prolonged, repeated exposures to the urine of a single mouse lead to enduring changes in the code?

Meanwhile, down the Atlantic coast, Rodriguez and his colleagues at Rockefeller have cloned what looks like the first bona fide human pheromone receptor. Using a combination of molecular approaches, they screened a human genomic library and found a sequence 28% identical to the mouse V1ra2 gene. This sequence, which the authors called V1RL1, contains key amino acid reisdues that are conserved in every rodent pheromone receptor, and is expressed predominantly in the human olfactory mucosa. Further studies will be needed to obtain definitive proof of the function of this receptor in pheromone detection. Hopefully, its ligand will not turn out to be a component of human urine.