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Are Pheromones Detected Through the Main Olfactory Epithelium?

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Abstract

A major sensory organ for the detection of pheromones by animals is the vomeronasal organ (VNO). Although pheromones control the behaviors of various species, the effect of pheromones on human behavior has been controversial because the VNO is not functional in adults. However, recent genetic, biochemical, and electrophysiological data suggest that some pheromone-based behaviors, including male sexual behavior in mice, are mediated through the main olfactory epithelium (MOE) and are coupled to the type 3 adenylyl cyclase (AC3) and a cyclic nucleotide-gated (CNG) ion channel. These recent discoveries suggest the provocative hypothesis that human pheromones may signal through the MOE.

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References

  1. Karlson P, Luscher M (1959) Pheromones’: a new term for a class of biologically active substances. Nature 183:55–56

    Article  PubMed  CAS  Google Scholar 

  2. Spehr M, Kelliher K, Li X, Boehm T, Leinders-Zufall T, Zufall F (2006) Essential role of the main olfactory system in social recognition of major histocompatibility complex peptide ligands. J Neurosci 26:1961–1970

    Article  PubMed  CAS  Google Scholar 

  3. Dulac C (1997) Molecular biology of pheromone perception in mammals. Semin Cell Dev Biol 8:197–205

    Article  PubMed  CAS  Google Scholar 

  4. Halpern M (1987) The organization and function of the vomeronasal system. Annu Rev Neurosci 10:325–362

    Article  PubMed  CAS  Google Scholar 

  5. Del Punta K, Leinders-Zufall T, Rodriguez I, Jukam D, Wysocki C, Ogawa S, Zufall F, Mombaerts P (2002) Deficient pheromone responses in mice lacking a cluster of vomeronasal receptor genes. Nature 419:70–74

    Article  PubMed  CAS  Google Scholar 

  6. Halpern M, Martinez-Marcos A (2003) Structure and function of the vomeronasal system: an update. Prog Neurobiol 70:245–318

    Article  PubMed  CAS  Google Scholar 

  7. Leypold B, Yu C, Leinders-Zufall T, Kim M, Zufall F, Axel R (2002) Altered sexual and social behaviors in trp2 mutant mice. Proc Natl Acad Sci USA 99:6376–6381

    Article  PubMed  CAS  Google Scholar 

  8. Stowers L, Holy T, Meister M, Dulac C, Koentges G (2002) Loss of sex discrimination and male–male aggression in mice deficient for TRP2. Science 295:1493–1500

    Article  PubMed  CAS  Google Scholar 

  9. Norlin E, Gussing F, Berghard A (2003) Vomeronasal phenotype and behavioral alterations in G alpha i2 mutant mice. Curr Biol 13:1214–1219

    Article  PubMed  CAS  Google Scholar 

  10. Restrepo D, Arellano J, Oliva A, Schaefer M, Lin W (2004) Emerging views on the distinct but related roles of the main and accessory olfactory systems in responsiveness to chemosensory signals in mice. Horm Behav 46:247–256

    Article  PubMed  CAS  Google Scholar 

  11. Meredith M (2001) Human vomeronasal organ function: a critical review of best and worst cases. Chem Senses 26:433–445

    Article  PubMed  CAS  Google Scholar 

  12. Wong S, Trinh K, Hacker B, Chan G, Lowe G, Gaggar A, Xia Z, Gold G, Storm DR (2000) Disruption of the type III adenylyl cyclase gene leads to peripheral and behavioral anosmia in transgenic mice. Neuron 27:487–497

    Article  PubMed  CAS  Google Scholar 

  13. Fulle H, Vassar R, Foster D, Yang R, Axel R, Garbers D (1995) A receptor guanylyl cyclase expressed specifically in olfactory sensory neurons. Proc Natl Acad Sci USA 92:3751–3755

    Article  Google Scholar 

  14. Belluscio L, Gold G, Nemes A, Axel R. (1998) Mice deficient in G(olf) are anosmic. Neuron 20:69–81

    Article  PubMed  CAS  Google Scholar 

  15. Dulac C, Axel R (1995) A novel family of genes encoding putative pheromone receptors in mammals. Cell 83:195–206

    Article  PubMed  CAS  Google Scholar 

  16. Herrada G, Dulac C (1997) A novel family of putative pheromone receptors in mammals with a topographically organized and sexually dimorphic distribution. Cell 90:763–773

    Article  PubMed  CAS  Google Scholar 

  17. Matsunami H, Buck L (1997) A multigene family encoding a diverse array of putative pheromone receptors in mammals. Cell 90:775–784

    Article  PubMed  CAS  Google Scholar 

  18. Ryba N, Tirindelli R (1997) A new multigene family of putative pheromone receptors. Neuron 19:371–379

    Article  PubMed  CAS  Google Scholar 

  19. Liman E, Corey D, Dulac C (1999) TRP2: a candidate transduction channel for mammalian pheromone sensory signaling. Proc Natl Acad Sci USA 96:5791–5796

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  21. Dulac C, Torello AT (2003) Molecular detection of pheromone signals in mammals: from genes to behaviour. Nat Rev Neurosci 4:551–562

    Article  PubMed  CAS  Google Scholar 

  22. Berghard A, Buck L, Liman E (1996) Evidence for distinct signaling mechanisms in two mammalian olfactory sense organs. Proc Natl Acad Sci USA 93:2365–2369

    Article  PubMed  CAS  Google Scholar 

  23. Mombaerts P (2004) Genes and ligands for odorant, vomeronasal and taste receptors. Nat Rev Neurosci 5:263–278

    Article  PubMed  CAS  Google Scholar 

  24. Trinh K, Storm DR (2003) Vomeronasal organ detects odorants in absence of signaling through main olfactory epithelium. Nat Neurosci 6:519–525

    PubMed  CAS  Google Scholar 

  25. Mandiyan V, Coats J, Shah N (2005) Deficits in sexual and aggressive behaviors in Cnga2 mutant mice. Nat Neurosci 8:1660–1662

    Article  PubMed  CAS  Google Scholar 

  26. Xu F, Schaefer M, Kida I, Schafer J, Liu N, Rothman DL, Hyder F, Restrepo D, Shepherd GM (2005) Simultaneous activation of mouse main and accessory olfactory bulbs by odors or pheromones. J Comp Neurol 489:491–500

    Article  PubMed  Google Scholar 

  27. Wang Z, Balet Sindreu C, Li V, Nudelman A, Guy C, Storm DR (2006) Pheromone detection in male mice depends on signaling through the type 3 adenylyl cyclase in the main olfactory epithelium. J Neurosci 26:7375–7379

    Article  PubMed  CAS  Google Scholar 

  28. Sam M, Vora S, Malnic B, Ma W, Novotny MV, Buck LB (2001) Neuropharmacology. Odorants may arouse instinctive behaviours. Nature 412:142

    Article  PubMed  CAS  Google Scholar 

  29. Hudson R, Distel H (1986) Pheromonal release of suckling in rabbits does not depend on the vomeronasal organ. Physiol Behav 37:123–128

    Article  PubMed  CAS  Google Scholar 

  30. Pfeiffer CA, Johnston RE (1994) Hormonal and behavioral responses of male hamsters to females and female odors: roles of olfaction, the vomeronasal system, and sexual experience. Physiol Behav 55:129–138

    Article  PubMed  CAS  Google Scholar 

  31. Dorries K, Adkins-Regan E, Halpern B (1997) Sensitivity and behavioral responses to the pheromone androstenone are not mediated by the vomeronasal organ in domestic pigs. Brain Behav Evol 49:53–62

    PubMed  CAS  Google Scholar 

  32. Pankevich DE, Baum MJ, Cherry JA (2004) Olfactory sex discrimination persists, whereas the preference for urinary odorants from estrous females disappears in male mice after vomeronasal organ removal. J Neurosci 24:9451–9457

    Article  PubMed  CAS  Google Scholar 

  33. Keller M, Douhard Q, Baum M, Bakker J (2006) Destruction of the main olfactory epithelium reduces female sexual behavior and olfactory investigation in female mice. Chem Senses 31:315–323

    Article  PubMed  Google Scholar 

  34. Liberles SD, Buck LB (2006) A second class of chemosensory receptors in the olfactory epithelium. Nature 442:645–650

    Article  PubMed  CAS  Google Scholar 

  35. Scott JW, Scott-Johnson PE (2002) The electroolfactogram: a review of its history and uses. Microsc Res Tech 58:152–160

    Article  PubMed  Google Scholar 

  36. Ottoson D (1956) Analysis of the electrical activity of the olfactory epithelium. Acta Physiol Scand 35 (Suppl 122):1–83

    Google Scholar 

  37. Kingston P, Zufall F, Barnstable C (1999) Widespread expression of olfactory cyclic nucleotide-gated channel genes in rat brain: implications for neuronal signalling. Synapse 32:1–12

    Article  PubMed  CAS  Google Scholar 

  38. Cheng K, Chan F, Huang Y, Chan W, Yao X (2003) Expression of olfactory-type cyclic nucleotide-gated channel (CNGA2) in vascular tissues. Histochem Cell Biol 120:475–481

    Article  PubMed  CAS  Google Scholar 

  39. Xia Z, Choi EJ, Wang F, Storm DR (1992) The type III calcium/calmodulin-sensitive adenylyl cyclase is not specific to olfactory sensory neurons. Neurosci Lett 144:169–173

    Article  PubMed  CAS  Google Scholar 

  40. Lin dY, Zhang S, Block E, Katz L (2005) Encoding social signals in the mouse main olfactory bulb. Nature 434:470–477

    Article  PubMed  CAS  Google Scholar 

  41. Kelliher KR, Chang YM, Wersinger SR, Baum MJ (1998) Sex difference and testosterone modulation of pheromone-induced NeuronalFos in the Ferret’s main olfactory bulb and hypothalamus. Biol Reprod 59:1454–1463

    Article  PubMed  CAS  Google Scholar 

  42. Woodley SK, Baum MJ (2004) Differential activation of glomeruli in the ferret's main olfactory bulb by anal scent gland odours from males and females: an early step in mate identification. Eur J Neurosci 20:1025–1032

    Article  PubMed  Google Scholar 

  43. O’Connell RJ, Meredith M (1984) Effects of volatile and nonvolatile chemical signals on male sex behaviors mediated by the main and accessory olfactory systems. Behav Neurosci 98:1083–1093

    Article  PubMed  CAS  Google Scholar 

  44. McClintock MK (1971) Menstrual synchrony and suppression. Nature 229:244–245

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  46. Gower DB, Ruparelia BA (1993) Olfaction in humans with special reference to odorous 16-androstenes: their occurrence, perception and possible social, psychological and sexual impact. J Endocrinol 137:167–187

    Article  PubMed  CAS  Google Scholar 

  47. Monti-Bloch L, Jennings-White C, Dolberg DS, Berliner DL (1994) The human vomeronasal system. Psychoneuroendocrinology 19:673–686

    Article  PubMed  CAS  Google Scholar 

  48. Jacob S, Hayreh DJ, McClintock MK (2001) Context-dependent effects of steroid chemosignals on human physiology and mood. Physiol Behav 74:15–27

    Article  PubMed  CAS  Google Scholar 

  49. Jacob S, McClintock MK, Zelano B, Ober C (2002) Paternally inherited HLA alleles are associated with women’s choice of male odor. Nat Genet 30:175–179

    Article  PubMed  CAS  Google Scholar 

  50. Monti-Bloch L, Grosser BI (1991) Effect of putative pheromones on the electrical activity of the human vomeronasal organ and olfactory epithelium. J Steroid Biochem Mol Biol 39:573–582

    Article  PubMed  CAS  Google Scholar 

  51. Berliner DL, Monti-Bloch L, Jennings-White C, Diaz-Sanchez V (1996) The functionality of the human vomeronasal organ (VNO): evidence for steroid receptors. J Steroid Biochem Mol Biol 58:259–265

    Article  PubMed  CAS  Google Scholar 

  52. Bhatnagar KP, Smith TD (2001) The human vomeronasal organ. III. Postnatal development from infancy to the ninth decade. J Anat 199:289–302

    Article  PubMed  CAS  Google Scholar 

  53. Trotier D, Eloit C, Wassef M, Talmain G, Bensimon JL, Doving KB, Ferrand J (2000) The vomeronasal cavity in adult humans. Chem Senses 25:369–380

    Article  PubMed  CAS  Google Scholar 

  54. Kinzinger JH, Johnson EW, Bhatnagar KP, Bonar CJ, Burrows AM, Mooney MP, Siegel MI, Smith TD (2005) Comparative study of lectin reactivity in the vomeronasal organ of human and nonhuman primates. Anat Rec A Discov Mol Cell Evol Biol 284:550–560

    PubMed  Google Scholar 

  55. Rodriguez I, Mombaerts P (2002) Novel human vomeronasal receptor-like genes reveal species-specific families. Curr Biol 12:R409–411

    Article  PubMed  CAS  Google Scholar 

  56. Meisami E, Mikhail L, Baim D, Bhatnagar KP (1998) Human olfactory bulb: aging of glomeruli and mitral cells and a search for the accessory olfactory bulb. Ann N Y Acad Sci 855:708–715

    Article  PubMed  CAS  Google Scholar 

  57. Rodriguez I, Greer CA, Mok MY, Mombaerts P (2000) A putative pheromone receptor gene expressed in human olfactory mucosa. Nat Genet 26:18–19

    Article  PubMed  CAS  Google Scholar 

  58. Lacazette E, Gachon AM, Pitiot G (2000) A novel human odorant-binding protein gene family resulting from genomic duplicons at 9q34: differential expression in the oral and genital spheres. Hum Mol Genet 9:289–301

    Article  PubMed  CAS  Google Scholar 

  59. Savic I, Berglund H, Gulyas B, Roland P (2001) Smelling of odorous sex hormone-like compounds causes sex-differentiated hypothalamic activations in humans. Neuron 31:661–668

    Article  PubMed  CAS  Google Scholar 

  60. Yoon H, Enquist LW, Dulac C (2005) Olfactory inputs to hypothalamic neurons controlling reproduction and fertility. Cell 123:669–682

    Article  PubMed  CAS  Google Scholar 

  61. Boehm U, Zou Z, Buck LB (2005) Feedback loops link odor and pheromone signaling with reproduction. Cell 123:683–695

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

This work was supported by the National Institute of Health grant DC04156.

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  1. Department of Pharmacology, University of Washington, Seattle, WA, 98195, USA

    Zhenshan Wang, Aaron Nudelman & Daniel R. Storm

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  1. Zhenshan Wang
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  2. Aaron Nudelman
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Correspondence to Daniel R. Storm.

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Wang, Z., Nudelman, A. & Storm, D.R. Are Pheromones Detected Through the Main Olfactory Epithelium?. Mol Neurobiol 35, 317–323 (2007). https://doi.org/10.1007/s12035-007-0014-1

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