Mammalian Pheromones


Pheromones are a vehicle for chemical communication in vertebrates and serve to relay information important for reproduction, mate selection, species and gender identification and social status. Activation of cellular signalling cascades in the vomeronasal organ combined with hormonal changes mediating reproduction are driven by pheromones that must be transduced from an external chemical message into an electrical signal read by the central nervous system.

Keywords: vomeronasal; olfaction; smell; mating; reproduction

Figure 1.

Anatomy of the olfactory system. (a) Odours, chemosignals and pheromones are captured in two different divisions of the olfactory system, the vomeronasal organ (VNO) and the main olfactory epithelium (MOE). The VNO is encapsulated by cartilage, contained within the intermaxillary bone, and is accessible to the external environment through the vomeronasal duct. The nasal passages of the MOE are comprised of turbinates that provide a large surface area for odorant binding and detection. OB, olfactory bulb, AOB, accessory olfactory bulb. (b) General, volatile odour molecules are detected in the MOE and this information is processed in the OB as the axons of the olfactory sensory neurons project across the cribriform plate into the brain. This information is then transmitted to the olfactory cortex, a higher brain region that includes the (AON), the (PC), the (OT), the (EC) and the (LA). Species‐specific pheromones and more specialized chemosignals are mostly detected in the VNO and this information is processed in the AOB and then propagates to the (VA) and then on to the (H) that controls endocrine and hormonal responses. Modified from Dulac and Torello (2003) Nature Publishing and Dr. Michael Meredith, (FSU), Program in Neuroscience, VNO website,

Figure 2.

Microscopic visualization of the vomeronasal organ (VNO) system. (a) Low‐ (left) and high‐ (right) magnification photomicrograph of a 10 μm frozen coronal section of the VNO. Four prominent structures are visible in the high‐magnification view as labelled: (C), vomeronasal (A), (VNE), and the (M). Bars,=25 μm. (b) Vomeronasal sensory neurons (VSNs) can be enzymatically dissociated from the VNE and these isolated neurons can be electrically stimulated with pheromones as in Figure . Visible in the photomicrograph are the filaments of the microvilli (M) that contain the pheromone transduction machinery (Figure ), a long modified (De) to carry electrical signals to the cell body or (S), and a portion of the (Ax), which will propagate the electrical signals to the brain, specifically to the AOB. Bar,=10 μm. (c) A coronal frozen section of the VNO labelled with a vital dye (rhodamine‐conjugated dextran) that is introduced into one of the vomeronasal ducts to visualize the VSNs. Note that the contralateral VNE is not labelled. (d) The dye was permitted to migrate for approximately 2 weeks in the animal to visualize the first site of synaptic connection into the AOB at the level of the (G). Photographs with permission from Murphy FA, Tucker K and Fadool DA (2001) Sexual dimorphism and developmental expression of signal‐transduction machinery in the vomeronasal organ. Journal of Comparative Neurology. 432: 61–74. Wiley‐Liss Inc. and Fadool DA, Wachowiak M and Brann JH (2001) Patch‐clamp analysis of voltage‐activated and chemically activated currents in the vomeronasal organ of Sternotherns odoratus (Stinkpot/musk turtle). Journal of Experimental Biology 204: 4199–4212. Company of Biologists Limited.

Figure 3.

Putative signal transduction machinery of the VNO. Pheromone molecules (purple diamond) are received at the external face of the VSN membrane by binding to a pheromone receptor that is a member of the seven transmembrane spanning (GPCR) family. The pheromone receptor undergoes a conformational change upon binding the pheromone and activates a G protein (green; either Gαo or Gαi2). The G protein in turn activates the effector enzyme (PLC) that acts to convert the substrate PIP2 to two different second messengers, diacyl glycerol (DAG) and inositol 1,4,5‐trisphosphate (IP3). There is evidence for the presence of three different ion channels that conduct calcium, namely the transient receptor potential channel (TRPC2), the type III IP3 receptor (IP3R3), and a nonselective cation channel that is activated by calcium (CaCN). The regulation and potential interaction of these three channels is currently under investigation to determine the source of the evoked electrical change in the VSN that encodes the information contained in the pheromone molecule. ER, endoplasmic reticulum; Homer, adaptor protein; CaM, calcium calmodulin; N,N‐terminus; C,C‐terminus. All of this transduction machinery is thought to reside at or in close proximity to the plasma membrane (mustard colour) of the microvilli.

Figure 4.

Segregation of VNO neural pathways in rodents. (a) Two classes of G‐protein coupled receptors, V1R and V2R, have been identified as putative pheromone receptors in the mammalian VNO. In rodents, the Gαi2 G protein is co‐localized with pheromone receptors of the V1R family and the Gαo G‐protein is co‐localized with receptors of the V2R family. The molecular structure of the pheromone molecule (purple diamond) is thought to be recognized by hypervariable transmembrane domains or a large extracellular N‐terminus in the V1R and V2R class of receptors, respectively. (b) The soma of the VSNs containing the V2R/Gαi2 combination (blue) are found in the basal region of the VNO and send their axonal projections to the posterior (P) portion of the AOB. In contrast, exhibiting anatomical and perhaps functional segregation, the V1R/Gαo combination (yellow) are found in the apical region of the VNO and send their axonal projections to the anterior (A) portion of the AOB.

Figure 5.

Patch‐clamp electrophysiology in the VNO. Electrical currents elicited from isolated VSN (as in Figure a) can be monitored through a technique called patch‐clamp recording. A recording electrode is fabricated from a glass capillary tube and an internal silver‐chloride wire is connected to an apparatus to capture and record currents as ions flow across the lumen of an ion channel protein in the membrane of the VSN. A stimulating glass pipette is positioned in close proximity to the VSN to deliver one of six different pheromones to the neuron at the tip of the microvilli/dendritic knob. A typical current response evoked by pheromone but not application of control saline is shown here. Note that the electrophysiological equipment can measure a biological current response in the VSN on the scale of picoamperes (10−12 A). For comparison, a light bulb operates in the milliampere range (10−3 A).


Further Reading

Dving KB and Trotier D (1998) Structure and function of the vomeronasal organ. The Journal of Experimental Biology 201: 2913–2925.

Dulac C and Torello AT (2003) Molecular detection of pheromone signals in mammals: From genes to behaviour. Nature Neuroscience Reviews 4: 551–562.

Frank Z, Kelliher KR and Leinders‐Zufall T (2002) Pheromone detection by mammalian vomeronasal neurons. Microscopy Research and Technique 58: 251–260.

Halpern M and Martínez‐Marcos A (2003) Structure and function of the vomeronasal system: An update. Progress in Neurobiology 70: 245–318.

Holy TE, Dulac C and Meister M (2000) Responses of vomeronasal neurons to natural stimuli. Science 289: 1569–1572.

Liman ER and Corey DP (1996) Electrophysiological characterization of chemosensory neurons from the mouse vomeronasal organ. The Journal of Neuroscience 16(15): 4625–4637.

Meredith M (2001) Human vomeronasal organ function: A critical review of best and worse cases. Chemical Senses 26: 433–445.

Also see:

Sacks O (1985) The Man who Mistook his Wife for a Hat. London: Duckworth.

Stern K and McClintock MK (1998) Regulation of ovulation by human pheromones. Nature 392: 177–179.

Trotier D and Doving KB (1998) “Anatomical description of a new organ in the nose of domesticated animals” by Ludvig Jacobson (1813). Chemical Senses 23: 743–754.

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How to Cite close
Fadool, Debra Ann(Sep 2005) Mammalian Pheromones. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0003379]