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.
Similar content being viewed by others
References
Karlson P, Luscher M (1959) Pheromones’: a new term for a class of biologically active substances. Nature 183:55–56
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
Dulac C (1997) Molecular biology of pheromone perception in mammals. Semin Cell Dev Biol 8:197–205
Halpern M (1987) The organization and function of the vomeronasal system. Annu Rev Neurosci 10:325–362
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
Halpern M, Martinez-Marcos A (2003) Structure and function of the vomeronasal system: an update. Prog Neurobiol 70:245–318
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
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
Norlin E, Gussing F, Berghard A (2003) Vomeronasal phenotype and behavioral alterations in G alpha i2 mutant mice. Curr Biol 13:1214–1219
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
Meredith M (2001) Human vomeronasal organ function: a critical review of best and worst cases. Chem Senses 26:433–445
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
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
Belluscio L, Gold G, Nemes A, Axel R. (1998) Mice deficient in G(olf) are anosmic. Neuron 20:69–81
Dulac C, Axel R (1995) A novel family of genes encoding putative pheromone receptors in mammals. Cell 83:195–206
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
Matsunami H, Buck L (1997) A multigene family encoding a diverse array of putative pheromone receptors in mammals. Cell 90:775–784
Ryba N, Tirindelli R (1997) A new multigene family of putative pheromone receptors. Neuron 19:371–379
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
Holy TE, Dulac C, Meister M (2000) Responses of vomeronasal neurons to natural stimuli. Science 289:1569–1572
Dulac C, Torello AT (2003) Molecular detection of pheromone signals in mammals: from genes to behaviour. Nat Rev Neurosci 4:551–562
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
Mombaerts P (2004) Genes and ligands for odorant, vomeronasal and taste receptors. Nat Rev Neurosci 5:263–278
Trinh K, Storm DR (2003) Vomeronasal organ detects odorants in absence of signaling through main olfactory epithelium. Nat Neurosci 6:519–525
Mandiyan V, Coats J, Shah N (2005) Deficits in sexual and aggressive behaviors in Cnga2 mutant mice. Nat Neurosci 8:1660–1662
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
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
Sam M, Vora S, Malnic B, Ma W, Novotny MV, Buck LB (2001) Neuropharmacology. Odorants may arouse instinctive behaviours. Nature 412:142
Hudson R, Distel H (1986) Pheromonal release of suckling in rabbits does not depend on the vomeronasal organ. Physiol Behav 37:123–128
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
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
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
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
Liberles SD, Buck LB (2006) A second class of chemosensory receptors in the olfactory epithelium. Nature 442:645–650
Scott JW, Scott-Johnson PE (2002) The electroolfactogram: a review of its history and uses. Microsc Res Tech 58:152–160
Ottoson D (1956) Analysis of the electrical activity of the olfactory epithelium. Acta Physiol Scand 35 (Suppl 122):1–83
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
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
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
Lin dY, Zhang S, Block E, Katz L (2005) Encoding social signals in the mouse main olfactory bulb. Nature 434:470–477
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
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
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
McClintock MK (1971) Menstrual synchrony and suppression. Nature 229:244–245
Stern K, McClintock MK (1998) Regulation of ovulation by human pheromones. Nature 392:177–179
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
Monti-Bloch L, Jennings-White C, Dolberg DS, Berliner DL (1994) The human vomeronasal system. Psychoneuroendocrinology 19:673–686
Jacob S, Hayreh DJ, McClintock MK (2001) Context-dependent effects of steroid chemosignals on human physiology and mood. Physiol Behav 74:15–27
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
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
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
Bhatnagar KP, Smith TD (2001) The human vomeronasal organ. III. Postnatal development from infancy to the ninth decade. J Anat 199:289–302
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
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
Rodriguez I, Mombaerts P (2002) Novel human vomeronasal receptor-like genes reveal species-specific families. Curr Biol 12:R409–411
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
Rodriguez I, Greer CA, Mok MY, Mombaerts P (2000) A putative pheromone receptor gene expressed in human olfactory mucosa. Nat Genet 26:18–19
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
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
Yoon H, Enquist LW, Dulac C (2005) Olfactory inputs to hypothalamic neurons controlling reproduction and fertility. Cell 123:669–682
Boehm U, Zou Z, Buck LB (2005) Feedback loops link odor and pheromone signaling with reproduction. Cell 123:683–695
Acknowledgment
This work was supported by the National Institute of Health grant DC04156.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12035-007-0014-1