A critical review of the evidence for the existence (1) human pheromones and (2) a functional vomeronasal organ (VNO) in humans
By Tim Jacob
Copyright Ó 1999 by
T.J.C. Jacob, School of Biosciences, Cardiff University, Cardiff CF10
Updated 29th November 2005
Index : Definitions , Historical Perspective , Androstadienone , Anatomy of the VNO , VNO structure , VNO receptors , VNO - functionality , Human pheromones , Odor and major histocompatibility complex , References , Summary
Pheromone-induced responses are mediated primarily by the vomeronasal organ (VNO). The VNO, also known as "Jacobson's organ", is part of an accessory olfactory system. It is present in a variety of non-human vertebrates but its existence in the human has been open to question until recently.
It was work published by Crosby and Humphrey (see below) that put the functional presence of the VNO in the human adult into doubt. In a standard anatomical textbook, "Correlative Anatomy of the Nervous System" by Crosby, Humphrey and Lauer (1962), we read the following; "In some human embryos, an accessory olfactory bulb, with complete representation of layering from the glomerular through the mitral cell layer, is to be found on the dorsomedial aspect of the main olfactory bulb (Humphrey, 1940). The accessory bulb receives the vomeronasal (or Jacobson's) nerve from the vestigial vomeronasal organ, which has also been demonstrated in the human embryo (McCotter, 1912). The vomeronasal nerve and its associated bulb vary in size and may be absent in the human embryo (Humphrey, 1940; Macchi, 1951). This variability appears to be characteristic of these structures in certain other adult primates (Lauer, 1945, 1949) Jacobson's organ and nerve and the accessory olfactory bulb are well developed in certain submammals and some subprimate mammals (Crosby and Humphrey, 1939). They are not present in adult man (Crosby and Humphrey, 1941). In human development these structures are merely ontogenetic signs of the persistence of phylogenetic structures and are without function".
Largely as a result of the above observations the existence of the VNO in humans has been disregarded. The consensus has been that, if it exists at all, it is vestigal and not functional. As recently as 1991 a paper by Meredith asserted that the accessory olfactory system is not present in humans or other old-world primates. This disregard for the existence of the VNO in adult humans is exemplified by the fact that the area containing the VNO is often removed during plastic surgery on the nose.
In 1980, Kreutzer and Jafek documented the early morphogenesis of the vomeronasal organ in the human embryo and early foetus. Later, in 1985, Johnson et al. examined 100 human adults specifically for the presence of the opening of the vomeronasal organ on the antero-interior part of the nasal septum. This was found in 39% of patients. Twenty seven human septums were removed post mortem, and vomeronasal structures were found in 70% of these. However, histological examination failed to reveal any evidence that these organs were functional (Johnson et al., 1985). In the same year, Nakashima et al. studied the VNO and nerves of Jacobson in a 28-week human foetus. They described the structure of the organ and traced the vomeronasal nervealong the nasal septum and through the cartilaginous cribriform plate with the olfactory nerve. While they found evidence for the existence of receptors in the vomeronasal epithelium similar to those in the olfactory epithelium, they suggested that the lack of intraepithelial blood vessels and mitotic figures in the epithelium indicated that the organ was undergoing degeneration at 28 weeks of gestation (Nakashima, Kimmelman and Snow, 1985). Since 1985 there has been a steady accumulation of evidence demonstrating the presence of the VNO in most, if not all, humans (Moran et al., 1985, 1991; Johnson et al., 1985; Stensaas et al., 1991; Garcia-Velasco and Mondragon, 1991, and reviewed in Moran et al., 1995).
the VNO (click for diagram)
The VNO is located bilaterally on the anterior third of the floor of the nasal septum. It opens into the nasal cavity by a pit which varies in size from 0.2 to 2 mm situated 1-2 cm from the posterior margin of the nostril.VNO structure
The VNO is lined by a pseudostratified, columnar epithelium some 60um in depth that lies on a thick basement membrane. The vomeronasal neuroepithelium contains three morphologically distinct cell types; basal cells, dark cells and light cells. The basal cells are small, polygonal, dark-staining cells, measuring 6um in diameter. The dark cells are tall, slender, columnar cells with densely staining cytoplasm. The light cells are tall, columnar cells that, like the dark cells, extend from the basement membrane to the free surface of the epithelium. They differ from the surrounding cells of the respiratory epithelium in the nose by having no cilia (Moran et al, 1995).
VNO - functionality
Is the adult human VNO vestigial?
Following the pioneering work on menstrual synchrony by McClintock (1971),
Stern and McClintock (1998) have shown that odourless axillary compounds
from the armpits of women in the late follicular phase of their menstrual
cycles accelerated the preovulatory surge of luteinizing hormone of recipient
women and shortened the menstrual cycles. Axillary compounds from the
same donors which were collected later in the menstrual cycle (at ovulation)
had the opposite effect: they delayed the luteinizing hormone surge of
the recipients and lenghtened their menstrual cycle (Stern and McClintock,
The definition of a pheromone (see above, Karlson and Luscher 1959) was
later modified to include a mutual benefit requirement (Rutowski, 1981).
In this context it is possible to see such mutual benefit if the pheromone
leads, for example, to choice of partner on the basis of their HLA-dependent
odortype to increase immune diversity (Ober et al., 1997, 1999) and lower
miscarriage rates (Ober et al., 1998) or if the pheromone participates
in the mother-infant bonding process (Schleidt, 1992). On its own it is
unlikely to be able to achieve these outcomes but, as recently reported
by Coureaud et al (2004), a pheromone can act as a reinforcing agent or
a one-trial conditioning agent in which the presence of the pheromone
converts a second odour (that of the partner or infant) into a conditioned
and major histocompatibility complex
While the behavioral changes induced by axillary secretions are supportive evidence, they have not convinced everyone in the field - measuring menstrual synchrony is a process fraught with problems. Receptors (or at least their mRNA) for pheromones have been found in the human olfactory epithelium, but we are still waiting for someone to demonstrate the presence of a pheromone receptor protein expressed in the surface membrane of an olfactory receptor neuron and that responds to a ligand (a potential pheromone) - as has been demonstrated for the olfactory receptors.
The case for human pheromones is still unproved - watch this space!
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