Same-Sex Attraction: The Science of Smell

Is There Biological Reasoning for Homosexuality?

male and female biological signs

Evidence supporting the biological reasoning for existence of homosexuality in the human species is growing. Even though there are still some who believe that homosexuality is a choice rather than an inborn trait, stemming either from a religious or conservative viewpoint, the recent research into pheromones has a reassuring sense about the overall biological explanation of homosexuality. Researchers continue to perform experiments on mice pheromones and organs involved in the detection of homosexual preferences, including consequent behavioral responses in mice, expanding the knowledge of human pheromones. This gives conclusive evidence to support the biological reasoning for homosexuality. The total effect of pheromones is uncertain and more research is underway, but there is enough data to support a mechanical pathway of determining the sexuality of human men. In the study of human pheromones, a chemical pathway has also been identified suggesting a train of reasoning for natural occurrences of homosexuality.

How Is This Hypothesis Being Tested

Mice have been the subjects of many studies which have been done to validate the same-sex attraction reasoning. There are many benefits to using mice as study samples: the mice are mammals with a wide array of olfactory genes coding for about 1,000 ORs and around 120 to 140 vomeronasal receptors. Mice can detect up to 100,000 compounds and there are at least six pheromones identified in the mouse urine (Buck 2004, Trinh & Storm 2004, Boschat et al. , 2002). Similarly, it is fairly easy to observe the pheromone-induced behaviors, and while in other mammals it may not always be the case, in mice the chemosensory communication is crucial to the survival and reproductive success of the animal. This means that, biologically, the protein-coding sequences of the DNA and the systems and organs used in chemosensory perception are highly conserved.

How do mice studies provide this “mechanical” and chemical insight into the existence of homosexuality in human males? There are two branches of research of mouse behavior that are of interest in respect to answering this question. Both of the branches include the VNO manipulations.

What Is the First Branch of Research?

The first branch of research involves surgical removal of the VNO at some point after maturation of the male mice. These mice have been compared with wild type mice that have undergone surgical procedure in which the VNO was not removed – known as sham surgery. In addition, the behavior of these animals has been compared to castrated mice as a way of providing a second control group since the behavior of castrated males has been studied and recorded in detail.

Pankewich, Baum, & Cherry (2004) conducted a study by comparing wild type mice with an intact VNO (labeled VNOi) and mice whose VNO has been removed (labeled VNOx). Both the control group – the wild-type mice – and the test group were put through the same surgical procedure as described above. In this study mice were tested by habituation-dishabituation tests. This involved testing the preference of males to male or female urinary odorants or the amount of time spent investigating each, and by comparing the mounting behavior of sexually experienced VNOi and VNOx towards castrated males and estrous females. Dishabituation is the term describing the initial interest in a particular odorant stimulus. Habituation is the term used when mice lose interest in that odorant after getting used to it.

VNOi and VNOx male mice were able to both detect and discriminate between the volatile urinary odors from intact males and estrous females. Thus, significant increases in investigation times (dishabituation) were seen in both groups of males during initial presentation of a urinary stimulus. Also, both groups showed significant increases in investigation times during the initial switch from male to estrous female urinary odors (or vice versa) presented outside the home cage. (Pankewich et al. , 2004, p.9453)

Similarly, once the mice were allowed to investigate the urinary odorants described above inside the cage, VNOi mice spent more time investigating the estrous female urine, while VNOx mice investigated both urine samples for equal duration of time.

A seemingly problematic section of the Pankewich et al. (2004) study is the report that both VNOi and VNOx males mount estrous females and castrated males at equal rates. But, the researchers do not go into detail in discussing their findings:

Figure 2 graphs

When VNOi and VNOx male mice were tested over a 1 month period with an estrous female and a castrated male (with intact male urine swabbed on the back) presented simultaneously, both groups “directed an equivalent (60-70%) percentage of their mounts toward the estrous female” (Pankewich et al. , 2004, p.9454).

Although, in this study, Pankewich et al. (2004) show interesting findings in regards to
the removal of the VNO from male mice.

In Figure 2, part C, in simultaneous presentation of urine the VNOx mice spend double the amount of time investigating intact male urine than estrous female urine (left part of the graph) when stimuli are outside the cage. Consequently, VNOx mice spend exact amount of time investigating both male and female urine while the stimulus is inside the cage.

Figure 1 graphs

In Figure 1, parts A, B, and C, although VNOx males spend equal amount of time investigating estrous and ovariectomized females, they spend more time than VNOi males in investigating both the castrated and intact male urines.

While this research study does prove that males with an uncompromised VNO are normal, it fails to prove that surgical manipulation of the VNO does not affect the male mice. Furthermore, while the title of the study includes that “olfactory sex discrimination persists” based on the fact that VNOx males “show no preference” for estrous females – their normal, expected results – the researchers stay conservative about implying that, according to their data, VNOx males seem to prefer investigating intact male urine to estrous female urine.

What Is the Second Branch of Research?

The second branch of research manipulates the effectiveness of the VNO by eliminating the genes for the receptors of pheromones on the DNA level. This manipulation leads us to one of the major lines of evidence as to how the functionality of the VNO affects the sexual behavior in mice. The following study shows why there should be a level of caution when examining studies on such genetically engineered specimens.

The study by Del Punta, Leinders-Zufall, Rodriguez, Jukam, Wysocki, & Ogawa, et al. (2002) attempted to genetically delete the V1R genes by chromosome engineering. The researchers tested female maternal aggression known to be dependent on the VNO, and four male behaviors including ultrasound vocaliziations, male-male aggression, male-male sexual behavior, and male-female sexual behavior. The researchers concluded:

First, mutant males have a reduced sexual drive and mutant females display a reduced level of maternal aggression. Second, their VNO exhibits specific chemosensory deficits… V1R ORF [open reading frame in DNA that codes for the gene] precludes axonal convergence to glomeruli [receiving neurons in the olfactory bulb]… As pheromones in other species often consist of blends of compounds that must be present in carefully balanced ratios to elicit distinct behaviors, the deletion of V1Ra and V1Rb gene families may produce specific avnosmias [handicaps] to certain cortical components leading to an altered representation of the blend in the brain and affecting behavior. Deletion of a V1R subset may ‘corrupt’ pheromone coding instead of blocking it. (Del Punta et al. , 2002, p.73).

The problem lies in the design of this experiment where a deletion of the gene caused unexpected results: the mutant mice were identical to the wild type in all aspects not connected to the VNO function. The mutant mice were inadequate in fully decoding the pheromonal messages.

Researchers in another study using similar techniques in genetic engineering had more success in blocking the pheromonal messaging by isolating a different protein
in the VNO neurons.

Using the tools of mouse genetics and multielectrode recording, we demonstrate that the sensory information of VNO neurons requires TRP2, a putative ion channel of the transient receptor potential family that is expressed exclusively in these neurons. (Stowers, Holy, Meister, Dulac, & Koentges, 2002. , p.1493).

The TRP2 protein is found in the microvilli of the VNO neurons, a “proposed site of pheromone sensory transduction” meaning that TRP2 plays a role in pheromone communication (Stowers et al. , 2002).

The researchers proposed that TRP2 may be the primary pathway for pheromonal signaling or it might act as a factor in additive fashion of pheromonal effect. They tested the importance of TRP2 by deleting the gene and comparing test subjects with the wild type mice.

The[se] results [of multielectrode testing] suggest that… genetic ablation of the TRP2 channel eliminates the sensory responses of VNO neurons to pheromonal cues… implying that TRP2… protein could be the primary conductance of the pheromone-evoked response, or it could act as an essential component of a multisubunit channel. (Stowers et al. , 2002, p.1495)

The same study examined mating behavior of TRP2-lacking mice. That study concludes that TRP2-lacking mice display mating behavior towards females as well as males based on their inability to discriminate between males and females due to inactivity of the VNO neurons in response to pheromone signaling. Stowers at al. (2002) effectively blocked the pheromonal pathway while not tampering with the formation of the proper neural connections between the VNO and the brain, unlike the Del Punta (et al. ) researchers.

Overall, these three mice studies show that a non-functional VNO disturbs the wild type behavior of mice, and because of a lack of correct pheromonal signaling these mice exhibit indiscriminate sexual behaviors and even show preference towards male-male interaction. Any mechanical tampering – surgical or genetic engineering – leading to a non-functional VNO or lack thereof can and usually does also lead to bi-sexual if not homosexual behavior in mice.

What Can Mice Teach Us about Human Sexuality?

As we have seen, a homosexual behavior can be induced manipulating the detection mechanism of pheromones in mice. Unfortunately, it is impossible to study pheromones in humans in the same fashion because of obvious ethical problems. Instead, researchers of the Kariolinska Institute in Sweden have isolated two chemicals proposed to be human pheromones and have conducted a study by comparing the effects of these chemicals on heterosexual men and women, and homosexual men. The data were obtained by two methods: positron emission tomography (PET) scans and magnetic resonance imaging (MRI) scans of the brain. PET is a common procedure used in medicine to detect certain diseases by scanning for tiny radioactive molecules administered to the patient intravenously. MRI is a similar procedure that scans the body with powerful magnets distinguishing among different tissues based on their density and magnetic resonance. The effects of two chemicals, previously mentioned 4, 16-androstadien-3-one (AND) a derivative of testosterone, and estra-1,3,5(10)16-tetraen-3-ol (EST) an estrogen-like steroid were compared to common odors and air. (Savic et al. , 2005)

The design of the experiment left nothing to chance. Twelve maximally gay men were compared to twelve straight women and twelve maximally straight men. Special testing was done to establish the sexuality of each test subject. Bloodwork was done each day at the same time of the day to test for levels of different hormones. The scanning was done at the same time of the day during which equal amount of time was spent smelling each of the odors. An excellent understanding of the human brain was described by researchers using several references. This description is necessary to understand the complete significance of the research. (Savic et al. , 2005) However, the two main areas of concern are the hypothalamus and olfactory cortex – regions discussed previously.

The hypothesis-based [region of interest] analysis showed that [homosexual men] processed AND congruently with [heterosexual women] rather than with [heterosexual men]… …The explorative statistical parametric mapping analysis confirmed that [heterosexual women] showed activation of the anterior hypothalamus with AND, whereas, in [heterosexual men], this area was recruited during smelling of EST. (Savic et al. , 2005, p.7359)

In retrospect, homosexual men and heterosexual women had similar responses to AND in the same way that heterosexual men responded to EST. Savic et al. point out in a previous study of effects of these chemicals on heterosexual students that they obtained similar results when students were smelling opposite sex stimuli whereas when these students smelled the same sex stimuli only the olfactory cortex of the brain was activated. (Savic-Berglund, 2004)

To explain these findings involves proposing the activation of two different pathways [of processing]: the ordinary olfactory response, which involves the olfactory tract and its usual connections, and another pathway activated by pheromones depending on the sex of the responder. (Savic-Berglund, 2004, p. 206)

The more recent study of these chemicals confirmed the researchers’ speculation about the effects of these chemicals, but not according to the sex of the test subject:

As discussed, signals form AND and EST seem to be bimodal, and primarily mediated either by the hypothalamus or by the olfactory regions. Consistent with the fact that both compounds were odorous, the conjunctional analysis showed involvement of olfactory areas even when hypothalamic pathway predominated. The major finding in the present study was that the preferred pathway in relation to the presented compound was associated with the responder’s sexual orientation (at least in men) rather than biological sex. (Savic et al, 2005, p.7359)

Dulac and Torello (2003) effectively discuss the overall significance of the combined pheromonal research in mice and humans in their discussion Box 1. They discuss the existence of key receptors (therefore genes) and organs that are involved in the detection of odors and pheromones.

Two large families of G-protein-coupled receptors that are expressed in the VNO and hypothesized to be pheromone receptors have been found in mouse and rat. However, most of the human orthologues of those genes seem to be non-functional pseudogenes… mining of the human genome[‘s] 200 sequences with homology to the V1R family… one has been found in the olfactory mucosa (Dulac & Torello, 2003, p.552)

Nonetheless, we have learned that the detection of olfactory stimuli is not solely ascribed to the main olfactory epithelium, and pheromones are effectively transported among individuals. However, because the human VNO doesn’t play as great a role in pheromone communication as it does in mice, the chance for a “corrupted” signaling pathway as a response to pheromones greatly increases to possibility of persistence of human homosexuality.

1 – Introduction to Pheromones

2 – Opposite-Sex Attraction

3 – Same-Sex Attraction

4 – Mother-Infant Bonding

5 – Menstrual Cycle Modulator

6 – Conclusion & References

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