Duke University Medical Center researchers demonstrated that genetic variants of odor receptors within the nose determine how a particular odor is perceived. The researchers, led by Duke's Hiroaki Matsunami, Ph.D., assistant professor of molecular genetics and microbiology, published the results of their experiments early online Sept. 16 in the journal Nature.

The researchers focused on two chemicals “ androstenone and androstadienone “ that are created naturally by the body during the breakdown of the male sex hormone testosterone and are excreted in sweat and urine.

We found that genetic variations of a specific odor receptor determine, to a significant degree, why the same chemicals smell pleasant or unpleasant to different people, Matsunami said. These results demonstrate the first link between the functioning of a human odor receptor gene and how that odor is perceived.

Humans have about 400 odor receptors within the nose that detect various odors or chemicals. Smells typically bind to their corresponding receptors, and the information is then relayed to the brain for processing.

The researchers wanted to uncover the reasons why people react differently when they smell these two sex steroid-derived chemicals. Hanyi Zhuang, a student in the Matsunami laboratory, tested all the known smell receptors in the laboratory and found one that reacted strongly with the two chemicals.

In conjunction with their collaborators at Rockefeller University, the researchers asked 391 volunteers to inhale the two chemicals and describe what they smelled. The results ranged from no smell at all, to descriptions such as vanilla and sweet and sickening and urine. DNA extracted from blood samples from each volunteer were sent to Matsunami's laboratory.

After performing genetic analysis on each of the samples and correlating the results with the smell descriptions, we were able to link specific genetic variants with specific perceptions, Matsunami said. While many theories of the different perceptions of smell focus on culture, experience or memory, our results show that an important portion of this variability is due to an individual's genes.

Matsunami added that these results will likely add to the debate over the existence of pheromones in humans. Pheromones are chemical signals between animals that express alarm, mating and navigation cues. In other species, they've been found to trigger behavioral changes in the smeller.

The sex-steroid odors that we tested in humans act as pheromones in pigs, and there has been debate whether these same chemicals act similarly in humans, Matsunami said. There is evidence that smelling these odors can affect the mood and physiological state of both men and women.

Matsunami and his colleagues plan further studies to understand how smelling these chemicals might affect human social and sexual behavior.

He added that there are likely other receptors and receptor variants that may also play roles in how these two chemicals are perceived. Since it is known that there are about 400 specific smell receptors and humans can detect more than 10,000 different odors, it follows that different combinations of receptor genes and variants must be involved in perceiving each odor, he said.

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