Researchers identify what could be human pheromone receptors

A new class of chemosensory receptors has been identified in the mouse olfactory epithelium by Drs. Linda Buck (who won the 2004 Nobel Prize for Physiology or Medicinefor her work on olfactory receptors and the organization of the olfactory system) and Stephen Liberles of the Fred Hutchinson Cancer research Center in Seattle, Washington.

The receptors, named trace amine-associated receptors (TAARs), mediate the identification of social cues in mice, and are also present in humans and fish. The paper describing the receptors was published online in Nature yesterday.

In situ hybridization using digoxygenin-labelled RNA antisense probes showed that 15 Taar genes are expressed in the olfactory epithelium of mice. Each Taar gene defines a unique subset of olfactory sensory neuron 15 genes in mice, but no evidence was found of Taar gene and odourant receptor gene co-expression in these cells.

Like odourant receptors, which are also expressed in the olfactory bulb, TAARs are G protein-coupled receptors. TAARs are not, however, related to odourant receptors – analysis of the DNA sequence showed that they are most closely related to receptors for the neurotransmitters dopamine and 5-hydroxytryptamine (5-HT, or serotonin), which are both biogenic amines.

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Receptor neurons in the Xenopus olfactory bulb.

Neither do TAARs have binding sites for odourant molecules, but instead bind small-molecule, volatile amines. One of the TAAR receptors binds to beta-phenylethylamine, an amine compound whose concentration in mouse urine is elevated in response to stress. At least three bind to isoamylamine, a pheromone found in the urine of male, but not female, mice.

Urine is a major source of social cues in mice and other organisms. Isoamylamine accelerates puberty in male mice; trimethylamine, another compound recognized by TAARs, is secreted in the urine of sexually mature male mice. Urine is also used by mice, dogs and other animals to mark territory. The authors suggest that these compounds elicit innate behaviours or physiological responses, which are mediated by TAARs, at least in mice.

TAARs are evolutionarily conserved in a diverse range of organisms. It has long been speculated that pheromones have an effect on the mating behaviour of humans, and this study provides some evidence that humans do, in fact, possess pheromone receptors.

Buck and Liberles have shown that humans have 6 Taar genes, and although they are “intrigued by the possibilty,” they hesitate to say that the mouse or human genes encode pheromone receptors. They are searching for molecules in human urine, sweat and vaginal secretions which might activate the receptors, but have not yet investigated the behavioural effects of knocking out one or more Taar genes.

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