Sex smells: pheromones in humans

Communicating with pheromones.

By the middle of the 20th century, biologists had become aware of a unique type of communication occurring among insects. The communication involved the secretion of substances that were similar to hormones in some ways, but also very different. While hormones are secreted into the bloodstream to elicit some reaction in the body, these newly identified substances exited the body and were used to elicit a reaction in a conspecific (another organism of the same species). They were given the name pheromones, from the Greek pherin (to transfer) and hormon (to excite).

Since that time, a number of pheromones have been identified in invertebrates and vertebrates alike. For example, when a honeybee hive is disturbed, guard bees produce a pheromone that alerts other bees in the hive; it encourages them to exit the hive and promotes aggressiveness. Beekeepers know all about this signal; they use smoke to calm an angry hive of bees because smoke inhibits receptors in bee antennae that detect the pheromone.

Pheromones that elicit a variety of behaviors have been identified in a number of species. Some pheromones, like those seen in bees, are used to call conspecifics together to attack or defend something, some aid in marking territory, and others leave trails that conspecifics can follow (to a stash of food, for example). Many pheromones also are associated with sex.

A large number of species, from microorganisms on up, release pheromones that play some role in mating. Some species of bacteria use pheromones to tell other bacteria to prepare to receive a transfer of genetic material in a very unromantic form of bacterial "sex" called conjugation. Even mammals, however, communicate with sex pheromones. Males of a number of species investigate the anogenital region of females with their nose, which contains a special pheromone-detector called the vomeronasal organ. Through exposure to pheromones, the male may be able to tell if the female is ovulating and will be receptive to his advances.

Although pheromones have been detected in many species, it has long been debated if they play any role in human communication. One reason that some have argued against an important role for pheromones in humans is that evidence suggests we don't have a functional vomeronasal organ. However, there do seem to be some examples of hidden chemical signaling between people.

Perhaps the best known putative pheromone mechanism in humans is the McClintock effect. The McClintock effect describes menstrual synchrony, which is when the menstrual cycles of women living in proximity to one another begin to synchronize, or start at around the same time. The effect was named after psychologist Martha McClintock, who hypothesized that pheromones were responsible for the synchronization.

The McClintock effect is controversial, and some argue that it isn't a real biological effect much less something caused by pheromones. But a number of other studies have also found indications of possible human pheromonal communication. From these studies, two steroids in particular have emerged as potential pheromones: androstadienone and estratetraenol.

Androstadienone, a metabolite of testosterone, is found in male semen and in secretions from the armpit area. Research has suggested it may promote physiological arousal in women, but not in heterosexual men. Estratetraenol, on the other hand, is an estrogen found in female urine. Estratetraenol has been found to affect autonomic arousal in men. Thus, some studies suggest (though this is still a controversial area) that androstadienone and estratetraenol are pheromones that contain some information detectable by the opposite sex.

A point-light walker used to demonstrate human gait.

A point-light walker used to demonstrate human gait.

A study to be published this month in Current Biology investigated information about gender that might be conveyed by these two putative pheromones. The investigators, Zhou et al., explored the effects of androstadienone and estratetraenol on the attribution of gender to point-light walkers (PLWs) displayed on a screen. PLWs are a collection of dots that represent human movement (see gif to the right). By changing settings, PLWs can adopt a more masculine or more feminine gait.

Zhou et al. exposed heterosexual and homosexual or bisexual men and women to either androstadienone, estratetraenol, or a control solution while viewing PLWs that displayed a spectrum of walking styles that ranged from a feminine gait to a masculine gait, with gender-neutral gaits falling in between the two. The participants, after watching the PLW walk very briefly, had to make a judgment as to whether the figure was masculine or feminine.

The researchers found that exposing heterosexual males to estratetraenol decreased the frequency of "male" responses, but it didn't affect ratings from heterosexual females. Exposing heterosexual females to androstadienone increased the frequency of "male" responses, but this didn't occur in heterosexual males. The results from the homosexual and bisexual groups were a little more ambiguous; estratetraenol didn't have an effect and androstadienone increased "male" responses in homosexual men but only to a gender-neutral PLW (and even then it was barely statistically significant).

Zhou et al. hypothesize that estratetraenol and androstadienone were biasing men and women, respectively, to discern the opposite sex in the movement of the PLWs. Thus, the authors argue that these substances convey information about masculinity and femininity. If true, what this means for everyday male-female interactions is unclear. The concentrations of the steroids that Zhou et al. used were much higher than you'd be exposed to just by standing next to someone on the subway.

So, there is much still to be learned about human pheromones. Even if androstadienone and estratetraenol are capable of communicating gender-specific information, their actual effect on human behavior today may be negligible. Thus, human pheromones may just be vestigial artifacts from our evolutionary history that we don't really have a use for anymore. On the other hand, there may be a complex system of communication occurring between people all the time that we are completely unaware of. And this system of communication could be shaping important decisions in your life, such as who you mate with, without your conscious realization.

Zhou, W., Yang, X., Chen, K., Cai, P., He, S., & Jiang, Y. (2014). Chemosensory Communication of Gender through Two Human Steroids in a Sexually Dimorphic Manner Current Biology DOI: 10.1016/j.cub.2014.03.035

Bisexuality in Drosophila

The fruit fly, like many organisms, has a stereotypical courtship ritual that precedes mating. After noticing a female, a male fly will follow her with a persistence that is strangely reminiscent to me of behavior that can be observed in any local pub on a busy night. The male will then tap the female with his foreleg, which allows him to sense her pheromones through chemoreceptors on his leg, and verify whether she is sexually receptive. If so, he will extend one wing and vibrate it, producing a species-specific courtship song. He also licks her genitalia to further test her pheromones. Of course these last few steps aren’t as noticeable at the local bar, and if they are you may be in the wrong place (perhaps a strange fetish pub). If she doesn’t reject him, he mounts her and attempts to copulate.

See the ritual here:

A fruit fly’s ability to discriminate between males and females is based on visual, auditory, and chemical cues, such as the pheromones 7-tricosene and cis-vaccenyl acetate (cVA). Flies that don’t produce these pheromones are deemed female and courted by other males. Mutant flies that cannot sense the pheromones attempt to copulate indiscriminately with males and females. Normally, however, homosexual behavior in Drosophila is relatively rare.

Earlier this year, a joint research team from France and America set out to determine what the biological difference between bisexual and heterosexual flies is. Is it that bisexual flies have difficulty sensing pheromones like 7-tricosone and cVA, or that they are sense the pheromones and are attracted to the opposite sex? What is the mechanism that causes that difference in attraction?

The group identified a mutation in drosophila that drastically increased homosexual encounters. They named it genderblind (gb) due to the resulting phenotype, which exhibited bisexual behavior. They determined, using an immunoblot, that the gb mutation causes a reduction in gb protein quantity. An immunoblot is also known as a western blot, and involves separating proteins with gel electrophoresis and then probing for specific proteins with antibodies that have been raised against them (presence of the protein will invoke an antibody response).

In order to determine if homosexual behavior in flies was simply a result of the misinterpretation of sensory cues, the group manipulated visual and chemosensory cues and measured fly response. They found that, although reducing the availability of visual cues affects the ability of the fly to discriminate between sexes, it was not enough of an effect to explain gb behavior. When they exposed the gb flies to mutant males that did not produce 7-tricosene and cVA, homosexual behavior was reduced to wild-type levels. When they applied these pheromones topically to the mutants, however, homosexual behavior from the gb flies was restored. This suggested that gb flies sense the pheromones, but interpret them differently than wild-type flies.

The group was able to identify the genderblind protein as a glial amino-acid transporter subunit and a regulator of glutamate in the central nervous system (CNS) of the fly. One function of glutamate is to reduce the strength of glutamatergic synapses through desensitization. The gb mutants had reduced genderblind protein levels and lower levels of extracellular glutamate. This resulted in increased glutamatergic synapse strength in the CNS. A glutamate antagonist administered to gb flies caused them to revert back to wild-type sexual behavior, indicating that the stimulation of glutamatergic circuits is responsible for the homosexual behavior. Additionally, inducing the overexpression of glutamate in the CNS of the fly caused an increase in homosexual behavior in both gb and wild-type flies.

Amazingly, the homosexual behavior could basically be turned on or off by manipulating glutamate transmission. The researchers suggest that this implies there is a physiological model for drosophila sexuality in which flies are pre-wired for both heterosexual and homosexual behavior. The homosexual behavior, however, is normally suppressed by genderblind proteins. A similar model has been proposed for mice.

So, the natural question is: what, if anything, does this say about homosexuality or bisexuality in humans? Well, the authors of the study state that genderblind has a high homology to a mammalian protein, the xCT protein. This is a cystine/glutamate transporter and may be an important regulator of glutamate in the CNS, similar to genderblind in the fly.

Despite this similarity, however, in my opinion it is improbable that a relationship between xCT protein levels and bisexuality/homosexuality that is similar to the one in drosophila and genderblind protein exists in humans. This isn’t to say there couldn’t be a correlation, just that the direct connection seen in fruit flies would appear too simple to be a basis for human sexual orientation, which is probably governed by a number of gene-protein relationships. So, while glutamate levels could play a part in suppressing homosexual behavior, they probably couldn’t act like a “bisexuality-switch” they way they do in the fruit fly.

 

Grosjean, Y., Grillet, M., Augustin, H., Ferveur, J., Featherstone, D.E. (2008). A glial amino-acid transporter controls synapse strength and courtship in Drosophila. Nature Neuroscience, 11 (1), 54-61. DOI:10.1038/nn2019