The secret codes of mammalian scents

Overview

David M. Ferrero, Stephen D. Liberles

Published Online: Jan 15 2010

DOI: 10.1002/wsbm.39

Full article on Wiley Online Library: HTML PDF

Can't access this content? Tell your librarian.

Abstract The scents of mammals are complex blends of natural products that reveal a wealth of individual information. Many mammals can decipher these scent codes to discern the gender, age, endocrine status, social status, and genotype of conspecifics using dedicated sensory receptors in their olfactory system. Among these social odors are pheromones, chemicals that trigger innate behaviors and physiological responses. Here, we review classes of mammal‐derived natural products that influence behavior through activation of the olfactory system. Copyright © 2009 John Wiley & Sons, Inc. This article is categorized under: Biological Mechanisms > Cell Signaling

This WIREs title offers downloadable PowerPoint presentations of figures for non-profit, educational use, provided the content is not modified and full credit is given to the author and publication.

Download a PowerPoint presentation of all images

Anatomy of the mouse olfactory system. The mouse olfactory system contains multiple subsystems, including the olfactory epithelium (OE), the vomeronasal organ (VNO), the Grueneberg ganglion (GG), and the septal organ (SO). Odorants enter the nasal cavity (NC) and access the OE during inhalation or the VNO by being pumped through a small duct. Sensory neurons of the OE, SO, and GG project to the main olfactory bulb (MOB), while sensory neurons of the VNO project to the accessory olfactory bulb (AOB). This image is adapted with permission from a previously published rendition of the olfactory system.2.

[ Normal View | Magnified View ]

Structures of some mammalian scent components. The chemical structures shown here correspond to entries in Figure 2, and include 1 (5α‐androst‐16‐en‐4‐one, a pheromone in boar saliva), 2 (4‐pregnene − 11β,21‐diol‐3,20‐dione 21‐sulfate, a sulfated steroid in mouse urine), 109 9 (trans − 2‐buten‐1‐thiol, a skunk odor constituent), 13a (α‐farnesene) and 13b (β‐farnesene). The natural configuration of the double bond in structure 10 is not reported, 60 and both enantiomers of structure 11 occur naturally.93.

[ Normal View | Magnified View ]

Examples of mammalian semiochemicals. We summarize reported findings on the biosynthesis and detection of prominent classes of mammal‐derived scent components discussed in the text. We expect this summary to be highly dynamic, as more information becomes available about known semiochemicals, and additional ligands are identified for the many orphan ORs, TAARs, V1Rs, and V2Rs across mammalian species. N/A indicates fields where data is not available.

[ Normal View | Magnified View ]

References

Brennan, PA, Zufall, F. Pheromonal communication in vertebrates. Nature 2006, 444: 308–315.
Buck, LB. The molecular architecture of odor and pheromone sensing in mammals. Cell 2000, 100: 611–618.
Burger, BV. Mammalian semiochemicals. Top Curr Chem 2005, 240: 231–278.
Dulac, C, Torello, AT. Molecular detection of pheromone signals in mammals: from genes to behaviour. Nat Rev Neurosci 2003, 4: 551–562.
Kelly, DR. When is a butterfly like an elephant? Chem Biol 1996, 3: 595–602.
Touhara, K. Molecular biology of peptide pheromone production and reception in mice. Adv Genet 2007, 59: 147–171.
Zufall, F, Leinders‐Zufall, T. Mammalian pheromone sensing. Curr Opin Neurobiol 2007, 17: 483–489.
Brennan, PA, Kendrick, KM. Mammalian social odours: attraction and individual recognition. Philos Trans R Soc Lond B Biol Sci 2006, 361: 2061–2078.
Singh, PB. Chemosensation and genetic individuality. Reproduction 2001, 121: 529–539.
Kobayakawa, K, Kobayakawa, R, Matsumoto, H, Oka, Y, Imai, T, et al. Innate versus learned odour processing in the mouse olfactory bulb. Nature 2007, 450: 503–508.
Halpern, M, Martinez‐Marcos, A. Structure and function of the vomeronasal system: an update. Prog Neurobiol 2003, 70: 245–318.
Mombaerts, P. Genes and ligands for odorant, vomeronasal and taste receptors. Nat Rev Neurosci 2004, 5: 263–278.
Dorries, KM, Adkins‐Regan, E, Halpern, BP. Sensitivity and behavioral responses to the pheromone androstenone are not mediated by the vomeronasal organ in domestic pigs. Brain Behav Evol 1997, 49: 53–62.
Hudson, R, Distel, H. Pheromonal release of suckling in rabbits does not depend on the vomeronasal organ. Physiol Behav 1986, 37: 123–128.
Keverne, EB. Importance of olfactory and vomeronasal systems for male sexual function. Physiol Behav 2004, 83: 177–187.
Lin, W, Arellano, J, Slotnick, B, Restrepo, D. Odors detected by mice deficient in cyclic nucleotide‐gated channel subunit A2 stimulate the main olfactory system. J Neurosci 2004, 24: 3703–3710.
Mandiyan, VS, Coats, JK, Shah, NM. Deficits in sexual and aggressive behaviors in Cnga2 mutant mice. Nat Neurosci 2005, 8: 1660–1662.
Restrepo, D, Arellano, J, Oliva, AM, Schaefer, ML, Lin, W. Emerging views on the distinct but related roles of the main and accessory olfactory systems in responsiveness to chemosensory signals in mice. Horm Behav 2004, 46: 247–256.
Wang, Z, Balet Sindreu, C, Li, V, Nudelman, A, Chan, GC, et al. Pheromone detection in male mice depends on signaling through the type 3 adenylyl cyclase in the main olfactory epithelium. J Neurosci 2006, 26: 7375–7379.
Brechbuhl, J, Klaey, M, Broillet, MC. Grueneberg ganglion cells mediate alarm pheromone detection in mice. Science 2008, 321: 1092–1095.
Fuss, SH, Omura, M, Mombaerts, P. The Grueneberg ganglion of the mouse projects axons to glomeruli in the olfactory bulb. Eur J Neurosci 2005, 22: 2649–2654.
Roppolo, D, Ribaud, V, Jungo, VP, Luscher, C, Rodriguez, I. Projection of the Gruneberg ganglion to the mouse olfactory bulb. Eur J Neurosci 2006, 23: 2887–2894.
Buck, L, Axel, R. A novel multigene family may encode odorant receptors: a molecular basis for odor recognition. Cell 1991, 65: 175–187.
Liberles, SD, Buck, LB. A second class of chemosensory receptors in the olfactory epithelium. Nature 2006, 442: 645–650.
Dulac, C, Axel, R. A novel family of genes encoding putative pheromone receptors in mammals. Cell 1995, 83: 195–206.
Herrada, G, Dulac, C. A novel family of putative pheromone receptors in mammals with a topographically organized and sexually dimorphic distribution. Cell 1997, 90: 763–773.
Matsunami, H, Buck, LB. A multigene family encoding a diverse array of putative pheromone receptors in mammals. Cell 1997, 90: 775–784.
Ryba, NJ, Tirindelli, R. A new multigene family of putative pheromone receptors. Neuron 1997, 19: 371–379.
Shi, P, Zhang, J. Comparative genomic analysis identifies an evolutionary shift of vomeronasal receptor gene repertoires in the vertebrate transition from water to land. Genome Res 2007, 17: 166–174.
Young, JM, Kambere, M, Trask, BJ, Lane, RP. Divergent V1R repertoires in five species: Amplification in rodents, decimation in primates, and a surprisingly small repertoire in dogs. Genome Res 2005, 15: 231–240.
Young, JM, Trask, BJ. V2R gene families degenerated in primates, dog and cow, but expanded in opossum. Trends Genet 2007, 23: 212–215.
Fleischer, J, Schwarzenbacher, K, Besser, S, Hass, N, Breer, H. Olfactory receptors and signalling elements in the Grueneberg ganglion. J Neurochem 2006, 98: 543–554.
Fleischer, J, Schwarzenbacher, K, Breer, H. Expression of trace amine‐associated receptors in the Grueneberg ganglion. Chem Senses 2007, 32: 623–631.
Tian, H, Ma, M. Differential development of odorant receptor expression patterns in the olfactory epithelium: a quantitative analysis in the mouse septal organ. Dev Neurobiol 2008, 68: 476–486.
Hu, J, Zhong, C, Ding, C, Chi, Q, Walz, A, et al. Detection of near‐atmospheric concentrations of CO2 by an olfactory subsystem in the mouse. Science 2007, 317: 953–957.
Leinders‐Zufall, T, Cockerham, RE, Michalakis, S, Biel, M, Garbers, DL, et al. Contribution of the receptor guanylyl cyclase GC‐D to chemosensory function in the olfactory epithelium. Proc Natl Acad Sci USA 2007, 104: 14507–14512.
Chamero, P, Marton, TF, Logan, DW, Flanagan, K, Cruz, JR, et al. Identification of protein pheromones that promote aggressive behaviour. Nature 2007, 450: 899–902.
He, J, Ma, L, Kim, S, Nakai, J, Yu, CR, Encoding gender and individual information in the mouse vomeronasal organ. Science 2008, 320: 535–538.
Holy, TE, Dulac, C, Meister, M. Responses of vomeronasal neurons to natural stimuli. Science 2000, 289: 1569–1572.
Lin, DY, Zhang, SZ, Block, E, Katz, LC. Encoding social signals in the mouse main olfactory bulb. Nature 2005, 434: 470–477.
Signoret, JP. Reproductive behaviour of pigs. J Reprod Fertil Suppl 1970, 11(Suppl 11) :105 + .
Melrose, DR, Reed, HC, Patterson, RL. Androgen steroids associated with boar odour as an aid to the detection of oestrus in pig artificial insemination. Br Vet J 1971, 127: 497–502.
Keller, A, Zhuang, H, Chi, Q, Vosshall, LB, Matsunami, H. Genetic variation in a human odorant receptor alters odour perception. Nature 2007, 449: 468–472.
Kelly, MJ, Wagner, EJ. Estrogen modulation of G‐protein‐coupled receptors. Trends Endocrinol Metab 1999, 10: 369–374.
Hara, TJ. Olfaction and gustation in fish: an overview. Acta Physiol Scand 1994, 152: 207–217.
Li, W, Scott, AP, Siefkes, MJ, Yan, H, Liu, Q, et al. Bile Acid secreted by male sea lamprey that acts as a sex pheromone. Science 2002, 296: 138–141.
Nodari, F, Hsu, FF, Fu, X, Holekamp, TF, Kao, LF, et al. Sulfated steroids as natural ligands of mouse pheromone‐sensing neurons. J Neurosci 2008, 28: 6407–6418.
Kakimoto, Y, Armstrong, MD. The phenolic amines of human urine. J Biol Chem 1962, 237: 208–214.
Del Punta, K, Leinders‐Zufall, T, Rodriguez, I, Jukam, D, Wysocki, CJ, et al. Deficient pheromone responses in mice lacking a cluster of vomeronasal receptor genes. Nature 2002, 419: 70–74.
Borowsky, B, Adham, N, Jones, KA, Raddatz, R, Artymyshyn, R, et al. Trace amines: identification of a family of mammalian G protein‐coupled receptors. Proc Natl Acad Sci USA 2001, 98: 8966–8971.
Grimsby, J, Toth, M, Chen, K, Kumazawa, T, Klaidman, L, et al. Increased stress response and beta‐phenylethylamine in MAOB‐deficient mice. Nat Genet 1997, 17: 206–210.
Paulos, MA, Tessel, RE. Excretion of beta‐phenethylamine is elevated in humans after profound stress. Science 1982, 215: 1127–1129.
Snoddy, AM, Heckathorn, D, Tessel, RE. Cold‐restraint stress and urinary endogenous beta‐phenylethylamine excretion in rats. Pharmacol Biochem Behav 1985, 22: 497–500.
Nishimura, K, Utsumi, K, Yuhara, M, Fujitani, Y, Iritani, A. Identification of puberty‐accelerating pheromones in male mouse urine. J Exp Zool 1989, 251: 300–305.
Price, MA, Vandenbergh, JG. Analysis of puberty‐accelerating pheromones. J Exp Zool 1992, 264: 42–45.
Gavaghan McKee, CL, Wilson, ID, Nicholson, JK. Metabolic phenotyping of nude and normal (Alpk:ApfCD, C57BL10J) mice. J Proteome Res 2006, 5: 378–384.
Blass, EM, Teicher, MH. Suckling. Science 1980, 210: 15–22.
Brake, SC. Suckling infant rats learn a preference for a novel olfactory stimulus paired with milk delivery. Science 1981, 211: 506–508.
Coureaud, G, Moncomble, AS, Montigny, D, Dewas, M, Perrier, G, et al. A pheromone that rapidly promotes learning in the newborn. Curr Biol 2006, 16: 1956–1961.
Schaal, B, Coureaud, G, Langlois, D, Ginies, C, Semon, E, et al. Chemical and behavioural characterization of the rabbit mammary pheromone. Nature 2003, 424: 68–72.
Belluscio, L, Gold, GH, Nemes, A, Axel, R. Mice deficient in G(olf) are anosmic. Neuron 1998, 20: 69–81.
Singh, PJ, Tucker, AM, Hofer, MA. Effects of nasal ZnSO4 irrigation and olfactory bulbectomy on rat pups. Physiol Behav 1976, 17: 373–382.
Singer, AG, Agosta, WC, O`Connell, RJ, Pfaffmann, C, Bowen, DV, et al. Dimethyl disulfide: an attractant pheromone in hamster vaginal secretion. Science 1976, 191: 948–950.
Novotny, M, Harvey, S, Jemiolo, B, Alberts, J. Synthetic pheromones that promote inter‐male aggression in mice. Proc Natl Acad Sci USA 1985, 82: 2059–2061.
Novotny, M, Jemiolo, B, Harvey, S, Wiesler, D, Marchlewska‐Koj, A. Adrenal‐mediated endogenous metabolites inhibit puberty in female mice. Science 1986, 231: 722–725.
Novotny, MV. Pheromones, binding proteins and receptor responses in rodents. Biochem Soc Trans 2003, 31: 117–122.
Novotny, MV, Jemiolo, B, Wiesler, D, Ma, W, Harvey, S, et al. A unique urinary constituent, 6‐hydroxy‐6‐methyl‐3‐heptanone, is a pheromone that accelerates puberty in female mice. Chem Biol 1999, 6: 377–383.
Leinders‐Zufall, T, Lane, AP, Puche, AC, Ma, W, Novotny, MV, et al. Ultrasensitive pheromone detection by mammalian vomeronasal neurons. Nature 2000, 405: 792–796.
Spehr, M, Kelliher, KR, Li, XH, Boehm, T, Leinders‐Zufall, T, et al. Essential role of the main olfactory system in social recognition of major histocompatibility complex peptide ligands. J Neurosci 2006, 26: 1961–1970.
Boschat, C, Pelofi, C, Randin, O, Roppolo, D, Luscher, C, et al. Pheromone detection mediated by a V1r vomeronasal receptor. Nat Neurosci 2002, 5: 1261–1262.
Sisk, CL, Foster, DL. The neural basis of puberty and adolescence. Nat Neurosci 2004, 7: 1040–1047.
Boehm, U, Zou, Z, Buck, LB. Feedback loops link odor and pheromone signaling with reproduction. Cell 2005, 123: 683–695.
Yoon, H, Enquist, LW, Dulac, C. Olfactory inputs to hypothalamic neurons controlling reproduction and fertility. Cell 2005, 123: 669–682.
Kimchi, T, Xu, J, Dulac, C. A functional circuit underlying male sexual behaviour in the female mouse brain. Nature 2007, 448: 1009–1014.
Datta, SR, Vasconcelos, ML, Ruta, V, Luo, S, Wong, A, et al. The Drosophila pheromone cVA activates a sexually dimorphic neural circuit. Nature 2008, 452: 473–477.
Stockinger, P, Kvitsiani, D, Rotkopf, S, Tirian, L, Dickson, BJ. Neural circuitry that governs Drosophila male courtship behavior. Cell 2005, 121: 795–807.
Boehm, T, Zufall, F. MHC peptides and the sensory evaluation of genotype. Trends Neurosci 2006, 29: 100–107.
Logothetis, NK, Sheinberg, DL. Visual object recognition. Annu Rev Neurosci 1996, 19: 577–621.
Brennan, PA. Outstanding issues surrounding vomeronasal mechanisms of pregnancy block and individual recognition in mice. Behav Brain Res 2009, 200: 287–294.
Falk, K, Rotzschke, O, Stevanovic, S, Jung, G, Rammensee, HG. Allele‐specific motifs revealed by sequencing of self‐peptides eluted from MHC molecules. Nature 1991, 351: 290–296.
Restrepo, D, Lin, W, Salcedo, E, Yamazaki, K, Beauchamp, G. Odortypes and MHC peptides: Complementary chemosignals of MHC haplotype? Trends Neurosci 2006, 29: 604–609.
Leinders‐Zufall, T, Brennan, P, Widmayer, P, Maul‐Pavicic, A, Jager, M, et al. MHC class I peptides as chemosensory signals in the vomeronasal organ. Science 2004, 306: 1033–1037.
Spehr, M, Spehr, J, Ukhanov, K, Kelliher, KR, Leinders‐Zufall, T, et al. Parallel processing of social signals by the mammalian main and accessory olfactory systems. Cell Mol Life Sci 2006, 63: 1476–1484.
Kelliher, KR, Spehr, M, Li, XH, Zufall, F, Leinders‐Zufall, T. Pheromonal recognition memory induced by TRPC2‐independent vomeronasal sensing. Eur J Neurosci 2006, 23: 3385–3390.
Leypold, BG, Yu, CR, Leinders‐Zufall, T, Kim, MM, Zufall, F, et al. Altered sexual and social behaviors in trp2 mutant mice. Proc Natl Acad Sci USA 2002, 99: 6376–6381.
Liman, ER, Corey, DP, Dulac, C. TRP2: a candidate transduction channel for mammalian pheromone sensory signaling. Proc Natl Acad Sci USA 1999, 96: 5791–5796.
Stowers, L, Holy, TE, Meister, M, Dulac, C, Koentges, G. Loss of sex discrimination and male‐male aggression in mice deficient for TRP2. Science 2002, 295: 1493–1500.
Ishii, T, Hirota, J, Mombaerts, P. Combinatorial coexpression of neural and immune multigene families in mouse vomeronasal sensory neurons. Curr Biol 2003, 13: 394–400.
Loconto, J, Papes, F, Chang, E, Stowers, L, Jones, EP, et al. Functional expression of murine V2R pheromone receptors involves selective association with the M10 and M1 families of MHC class Ib molecules. Cell 2003, 112: 607–618.
Singh, PB, Brown, RE, Roser, B. MHC antigens in urine as olfactory recognition cues. Nature 1987, 327: 161–164.
Humphries, RE, Robertson, DH, Beynon, RJ, Hurst, JL. Unravelling the chemical basis of competitive scent marking in house mice. Anim Behav 1999, 58: 1177–1190.
Bocskei, Z, Groom, CR, Flower, DR, Wright, CE, Phillips, SE, et al. Pheromone binding to two rodent urinary proteins revealed by X‐ray crystallography. Nature 1992, 360: 186–188.
Timm, DE, Baker, LJ, Mueller, H, Zidek, L, Novotny, MV. Structural basis of pheromone binding to mouse major urinary protein (MUP‐I). Protein Sci 2001, 10: 997–1004.
Beynon, RJ, Hurst, JL. Multiple roles of major urinary proteins in the house mouse, Mus domesticus. Biochem Soc Trans 2003, 31: 142–146.
Novotny, MV, Ma, W, Wiesler, D, Zidek, L. Positive identification of the puberty‐accelerating pheromone of the house mouse: the volatile ligands associating with the major urinary protein. Proc Biol Sci 1999, 266: 2017–2022.
Hurst, JL, Payne, CE, Nevison, CM, Marie, AD, Humphries, RE, et al. Individual recognition in mice mediated by major urinary proteins. Nature 2001, 414: 631–634.
More, L. Mouse major urinary proteins trigger ovulation via the vomeronasal organ. Chem Senses 2006, 31: 393–401.
Mudge, JM, Armstrong, SD, McLaren, K, Beynon, RJ, Hurst, JL, et al. Dynamic instability of the major urinary protein gene family revealed by genomic and phenotypic comparisons between C57 and 129 strain mice. Genome Biol 2008, 9: R91.
Shahan, K, Denaro, M, Gilmartin, M, Shi, Y, Derman, E. Expression of six mouse major urinary protein genes in the mammary, parotid, sublingual, submaxillary, and lachrymal glands and in the liver. Mol Cell Biol 1987, 7: 1947–1954.
Shaw, PH, Held, WA, Hastie, ND. The gene family for major urinary proteins: expression in several secretory tissues of the mouse. Cell 1983, 32: 755–761.
Hastie, ND, Held, WA, Toole, JJ. Multiple genes coding for the androgen‐regulated major urinary proteins of the mouse. Cell 1979, 17: 449–457.
Knopf, JL, Gallagher, JF, Held, WA. Differential, multihormonal regulation of the mouse major urinary protein gene family in the liver. Mol Cell Biol 1983, 3: 2232–2240.
Briand, L, Trotier, D, Pernollet, JC. Aphrodisin, an aphrodisiac lipocalin secreted in hamster vaginal secretions. Peptides 2004, 25: 1545–1552.
Krieger, J, Schmitt, A, Lobel, D, Gudermann, T, Schultz, G, et al. Selective activation of G protein subtypes in the vomeronasal organ upon stimulation with urine‐derived compounds. J Biol Chem 1999, 274: 4655–4662.
Luo, M, Fee, MS, Katz, LC. Encoding pheromonal signals in the accessory olfactory bulb of behaving mice. Science 2003, 299: 1196–1201.
Kimoto, H, Haga, S, Sato, K, Touhara, K. Sex‐specific peptides from exocrine glands stimulate mouse vomeronasal sensory neurons. Nature 2005, 437: 898–901.
Kimoto, H, Sato, K, Nodari, F, Haga, S, Holy, TE, et al. Sex‐ and strain‐specific expression and vomeronasal activity of mouse ESP family peptides. Curr Biol 2007, 17: 1879–1884.
Haga, S, Kimoto, H, Touhara, K. Molecular characterization of vomeronasal sensory neurons responding to a male‐specific peptide in tear fluid: sexual communication in mice. Pure Appl Chem 2007, 79: 775–783.
Hsu, FF, Nodari, F, Kao, LF, Fu, X, Holekamp, TF, et al. Structural characterization of sulfated steroids that activate mouse pheromone‐sensing neurons (dagger). Biochemistry 2008, 47: 14009–14019.
Sam, M, Vora, S, Malnic, B, Ma, W, Novotny, MV, et al. Neuropharmacology. Odorants may arouse instinctive behaviours. Nature 2001, 412: 142.
Trinh, K, Storm, DR. Vomeronasal organ detects odorants in absence of signaling through main olfactory epithelium. Nat Neurosci 2003, 6: 519–525.
Meredith, M, O`Connell, JR. HRP uptake by olfactory and vomeronasal receptor neurons: use as an indicator of incomplete lesions and relevance for non‐volatile chemoreception. Chem Senses 1988, 13: 487–515.

Access to this WIREs title is by subscription only.

Recommend to Your
Librarian Now!

The secret codes of mammalian scents

Browse by Topic

Access to this WIREs title is by subscription only.

The latest WIREs articles in your inbox