Biology 202
1999 Final Web Reports
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Sixth Sense: The Vomeronasal Organ

Jason Bernstein

"We are all more influenced by smell than we know." (Hercule Poirot)
....Murder in Retrospect, Agatha Christie

Biologists have long realized that the noses of most vertebrates actually contain two sensory channels. The first is the familiar olfactory system, which humans possess. The second channel is the vomeronasal complex, a system that has its own separate organs, nerves, and connecting structures in the brain. The function of the vomeronasal system is the detection of pheromones, chemical messengers that carry information between individuals of the same species. It was widely believed (as I found in some of the older texts I examined) that humans had long ago discarded this sensory system somewhere along evolution's trail. But convincing behavioral and anatomical evidence has since brought the notion of a human vomeronasal organ (VNO) into the realm of scientific fact. Some thirty years ago, when anatomist David Berliner was studying human skin composition using scraped skin cells from the insides of discarded casts, he found that when he left vials containing skin extracts open, his lab assistants would become more friendly and warm than usual (1). When, months later, he decided to cover the vials, the warm and relaxed behavior was noticeably reduced. These findings led him to investigate the possible existence of odorless human pheromones and a "sixth sense" organ to detect their presence, a VNO.

While this early evidence was not empirical, anatomists have since found that all humans display two tiny pits, with duct openings, on both sides of the septum just behind the opening of the nose (3). The duct leads into a tubular lumen lacking a thick, distinct sensory epithelium. However, there are cells in the lining of the lumen that may be VNO receptor neurons. They appear to be bipolar neurons and respond to neuron specific stains (2). In a recent experiment, human VNO was reported to respond positively (by emitting electrical signals) to puffs of air laden with substances claimed to be human pheromones (2). If the experiment is valid, it presents strong evidence supporting the hypothesis that the human VNO is functioning, not vestigial. In some respects, however, the proof is lacking. The human VNO lacks the characteristic capsule and large blood vessels of other mammals' VNOs (2). The sensory epithelium, as mentioned earlier, is not well developed. In addition, connections between the presumed VNO receptor neurons and the brain have not yet been confirmed in humans. In other mammals, nerve impulses from the sensory cells of the vomeronasal organ enter brain structures known as the accessory olfactory bulbs and also project to brain structures that regulate sexual behavior and the secretion of gonadotropin, a pituitary hormone regulating the function of the testes (4). The accessory olfactory bulb, the normal termination of vomeronasal receptor-neuron axons (i.e. the doorway to the brain for these signals), cannot be distinguished clearly in the human brain (2). But, the structural inconsistencies (shortcomings?) of the human VNO system do not prove that it is inactive. They merely indicate that it different, and perhaps less fundamental, than in our fellow vertebrates, a notion that is readily apparent from more cursory observations. Recent human behavioral studies, which will be discussed later, have tipped the conventional wisdom scales (for this still somewhat mysterious and understudied topic) to the viewpoint supporting the presence of a functioning human VNO.

The VNOs of other vertebrates, thankfully, are somewhat less mysterious. This is, in part, because the anatomy and function of the VNO in snakes, some lizards, and nonprimate mammals are less disguised than in humans. It is also related to the ease with which researchers can remove or disable the VNOs of animals for experimentation. In humans, this highly invasive and damaging procedure is, for obvious reasons, not feasible.

Because the vomeronasal organ in non-human animals is typically situated in a pouch off the nasal cavity, airborne odorant molecules cannot efficiently enter the dead-end passage the same way that they reach the olfactory receptor cells (4). The VNO requires another delivery system. In snakes, environmental stimuli enter the vomeronasal organ through ducts that connect it with the oral cavity. During flicking, the tongue picks up molecules from the air and nearby objects. As the tongue retracts into the mouth at the end of each flick, the molecules are drawn over the duct openings leading to the VNO (2). Mammals have evolved a different delivery system. When they lick and sniff, molecules from the environment are absorbed onto the nose and tongue, and are then transported into the vomeronasal organ in saliva. A pumping action that dilates and constricts the organ walls increases the motion of fluid in and out of the dead-end structure, moving stimuli rapidly into the chamber (2).

Vomeronasal sensory neurons are distinct from olfactory neurons in their morphology (olfactory neurons have cilia, vomeronasal neurons have microvilli) and in the signal transduction components that they express (5). The main olfactory system of mammals recognizes the universe of odorants using as many as a thousand related G protein-coupled receptors (5). Oddly enough, the sensory potential of this vast family is not exploited by the mammalian vomeronasal organ. Vomeronasal neurons do not express the classical olfactory receptors. In a 1995 study by Dulac and Axel, VNO neuron receptors(the animal species was not specified) were identified using a single-cell PCR strategy to find genes expressed at high levels (5). They found a family of 30-100 genes that encode proteins that are completely unrelated to the olfactory receptors. Only one or a few receptor proteins are expressed per cell, indicating possible cellular specificity to molecular stimulants.

A majority of the research on vomeronasal function has been in rodents and snakes, and most has involved lesions of the vomeronasal or olfactory systems in order to reveal deficits in behavior or physiological function. In rodents, pheromone communication can produce dramatic effects on reproductive behavior and physiology and can be the basis for aggressive behavior. Many of these effects depend on chemosensory input from the VNO. For example, male mice and other rodents produce chemosignals that accelerate puberty in immature females of the same species (2). Female mice living in groups produce a urinary chemosignal that suppresses estrus in other females. In both of these cases, removal of the VNO prevents the response (2). There is evidence that these effects are due to an influence of VNO input on hormone levels. In many species, both sexes show changes of luteinizing-hormone (LH) in response to chemical signals from opposite sex individuals (2). In mice and hamsters, removal of the VNO prevents the hormonal changes (LH and testosterone) normally observed after exposure of males to female chemosignals. When LH is injected into the brain, deficits in mating behavior caused by VNO removal are restored. Furthermore, in sexually naive mice and hamsters, the removal of the vomeronasal organs alone prevents mating behavior, while removal of the olfactory input alone does not (4). This is strong evidence that the VNO plays a critical role in facilitating certain preprogrammed behaviors in these mammals.

Knowing that the VNO system acts as an intermediary between chemical stimuli and the transmission of behavioral instructions, we should address how this is facilitated by neural wiring. The VNO receptor neurons have axons that leave the VNO capsule in bundles and carry electrical signals to the accessory olfactory bulb (AOB). The AOBs process VNO input and lie dorsal to the main olfactory bulbs, processors of smell input. The VNO information from the AOB and the olfactory information from the MOB are carried via separate sets of "second-order" axons to the amygdala (2). From there the VNO system projects directly to the preoptic area and to the hypothalamus, areas known to be involved in reproductive behavior (2). Recent experiments indicate that the VNO-recipient area of the amygdala and the preoptic area are active during VNO-initiated male hamster mating behavior, and that the amygdala is activated when animals are stimulated by female pheromones. The main olfactory system did not show activation beyond control levels during pheromone stimulation (2).

So, what role, if any, does consciousness play our model of the VNO system? There is apparently no neocortical projection of the vomeronasal system. Based partly on this evidence that it bypasses the cerebral cortex, it has been suggested that vomeronasal sensory input may be unavailable to conscious processes (6). In other words, the recipient of pheromonal communication, despite exhibiting a behavioral response, may be unaware of the stimulus. This hypothesis is not yet provable. First, while the cerebral cortex is thought to be the location of conscious thought, it is likely that many brain structures integrate to create consciousness. As we know, the brain typically has several ways of fulfilling a given task, and consciousness is probably a particularly complex, demanding task, likely requiring the cooperation of various structures. We also don't know that rodents and other VNO possessing creatures have conscious awareness in the first place (at least the way we humans do). We cannot yet prove that they have an "I" function, a self that can think and feel. However, the concept that a higher organisms such as rodents or bears could have a highly developed, behavior-altering sense of which they are not "aware" is fascinating, and worthy of further exploration.

There is no question that humans are not aware of this sixth sense, if they do indeed have it. If we do receive chemical signals from people in our vicinity, these signals must compete with many other factors that influence our behavior. Yet our physiology may respond similarly to that of other mammals. Researchers at the Monell Chemical Senses Center in Philadelphia studying the effects of male odors on hormone levels in females have found that the length and timing of the menstrual cycle are markedly influenced by odors from the underarms of males (7). These responses could be linked to the observation that the menstrual cycle of women living around men tends to be more regular. Another study has indicated that the long observed phenomenon of women living in close quarters developing synchronized menstrual cycles may be explained by the recognition of pheromones by the VNO (7). The researchers wiped pads (which had been placed under women's armpits for 8 hours) under the noses of female subjects. They found that "compounds donated by women in the late follicular phase (the early portion) of their menstrual cycles accelerated the preovulatory surge of luteninizing hormone (LH) of recipient women, and shortened their menstrual cycles." They also found that "compounds from the same donors, but collected later (at the time of ovulation) had an opposite effect, delaying the LH surge of recipients and lengthening their menstrual cycles." As compelling as the evidence is, neither case proves that the VNO is involved in the physiological responses. However, some sort of sensory processing at an unconscious level must be taking place to bring about these responses, and the VNO appears to be at the root of it.

If the human pheromonal system exists, it is logical to assume that it has an adaptive purpose. While every existing biological system does not necessarily have an adaptive purpose, evolutionary theory suggests that a species living in a unstable environment will, through thousands of generations, be trimmed of what is not beneficial to survival. It has been proposed that the purpose of the pheromonal system is not to attract the opposite sex, but to inform the individual reproductive system of the continued presence of a mate (8). There is no real need for humans to use odors to attract the opposite sex: we have excellent hearing and eyesight and can recognize each other at long distances. Males and females are easy to differentiate because they have distinctive shapes. We live in groups, and can thus easily establish initial contact with potential mates. Many of the animals which rely on odors and pheromones to attract, find, and recognize mates live in environments (like burrows, thick brush, darkness, etc.) in which meeting mates is much less convenient.

Let's consider the conditions under which humans are close enough to smell, (or perceive) the bodily emanation of another. This occurs through close contact, such as sleeping or cuddling with mates or potential mates. Perhaps, then, the human VNO and pheromonal system serves to promote and maintain pair bonds, or increase the probability that such a relationship will lead to reproduction (8). So, how might this be selected for? If the effect of male pheromonal cues was to make the female more fertile, there would indeed be selection for male ability to emit the pheromones, and for female ability to receive them. Males who lacked the mechanism for releasing the pheromones (smaller apocrine glands, less underarm or genital hairs, lack of necessary hormones) would produce fewer offspring from their matings. Females who lacked the apparatus for receiving the male pheromonal signals would be unable to adjust their fertility based on the presence or absence of a male, and would be out-reproduced by those females who did receive the signals (8). If males transmit pheromonal signals while cuddling with or sleeping with females, then it could help explain why humans are unusually sexual animals engaging in much non-reproductive sex, including copulation when the female is not in the fertile portion of her menstrual cycle. If sexual contact serves to increase female fertility as the evidence suggests, it would help explain the selection for male and female desires for frequent sex.

There is anatomical, behavioral, physiological, and adaptive evidence for a human VNO. Research merely needs to take a final step, to witness the VNO in action. Human pheromones must also be structurally identified and better understood for the picture to be complete. It is likely that future textbooks will attribute to humans this mysterious, unconscious sixth sense.

WWW Sources

1)Chemicals the cause excitement

2)VNO website

3)Science Frontiers article

4)Chemical Communication by Willam C. Agosta

5) Olfactory Receptors, Vomeronasal Receptors, and the Organization of Olfactory Information. From Cell, a journal

6)Howard Hughes olfactory website

7)Article from The Scientist

8)Pheromone Book Review

Additional Sources

Messages sent through sweat

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This paper reflects the research and thoughts of a student at the time the paper was written for a course at Bryn Mawr College. Like other materials on Serendip, it is not intended to be "authoritative" but rather to help others further develop their own explorations. Web links were active as of the time the paper was posted but are not updated.

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