Feromonas

Neuron, Vol. 46, 699–702, June 2, 2005, Copyright ©2005 by Elsevier Inc. DOI 10.1016/j.neuron.2005.04.032

What Is a Pheromone? Mammalian Pheromones Reconsidered
Lisa Stowers2,* and Tobias F. Marton1 1 University of California San Diego, California 92093 2 Department of Cell Biology The Scripps Research Institute 10550 North Torrey Pines Road La Jolla, California 92037

MinireviewPheromone communication is a two-component system: signaling pheromones and receiving sensory neurons. Currently, pheromones remain enigmatic bioactive compounds, as only a few have been identified, but classical bioassays have suggested that they are nonvolatile, activate vomeronasal sensory neurons, and regulate innate social behaviors and neuroendocrine release. Recent discoveries of potentialpheromones reveal that they may be more structurally and functionally diverse than previously defined. Pheromones Are a Mystery Pheromones are unlike the familiar chemical odorants that generate our perception of smell and subtly guide our behavior. With experience, we learn to be drawn to the aroma of finely prepared food and repelled when it has spoiled. But, in addition to the seemingly limitlessodorant combinations that we associate with certain behavioral outcomes, most terrestrial vertebrates also respond to pheromones. These semiochemicals are classically defined as chemical cues emitted and detected by individuals of the same species that influence social and reproductive behavior. A naive animal responds behaviorally to the presence of pheromones without any prior experience orexposure: pups suckle, males fight, and estrus cycles are altered. And yet, despite the importance of these chemical cues in regulating essential animal behaviors, the nature of these elusive ligands remains largely unknown. A growing body of evidence indicates that the structural and functional characteristics of pheromones may be far more diverse than revealed by classical experiments. Recent studies(Leinders-Zufall et al., 2000; Lin et al., 2005) in conjunction with prior evidence suggest that the working definition of pheromones as nonvolatile molecules that regulate innate social behavior by activating vomeronasal organ (VNO) sensory neurons may be too restrictive. Indeed, it appears that pheromones may be nonvolatile or ephemeral, activate VNO or main olfactory epithelium (MOE) neurons, andmay have their effects altered by context as opposed to being strictly innate. Are Pheromones Simply Ligands that Activate the Vomeronasal Organ? Two-hundred years ago, Jacobson described an anatomically distinct organ within the nasal cavity filled with chemoreceptive cells and, without supporting evidence, dubbed it the “sexual nose” as a potential mediator of the pheromone response (Cuvier,1811). Subse*Correspondence: stowers@scripps.edu

quent experiments have suggested that the sexual nose, now referred to as the vomeronasal organ, responds to pheromones while chemoreceptive neurons that reside in the main olfactory epithelium initiate the perception of odorants (Figure 1). More recently, molecular characterization has revealed that the primary signal transduction machinery of MOEneurons is distinct from that of VNO neurons (reviewed in Dulac and Torello, 2003). Although ligands for both structures activate specific G protein-coupled receptors (GPCRs), the MOE receptors are evolutionarily distinct from all identified VNO receptors. Furthermore, GPCR activation in the MOE leads to the production of cAMP to gate CNGA2 channels. These signaling components are not expressedin VNO neurons that instead utilize a phospholipase C pathway to activate TrpC2 channels. Most interesting, however, is the apparent segregation of the neuronal circuitry. MOE neurons project axons to the olfactory bulb and synapse on mitral cells that in turn signal to the cortex and the olfactory amygdala. In contrast, VNO neurons project to the accessory olfactory bulb and relay their signal...