The Hypothalamus Doesn't Lie

What is at the root of homosexuality? This question has divided families, religious denominations, and even entire societies over the years, particularly in recent times. Is it nature (inborn) or nurture (environmental)? Genetics and prenatal hormones? A distant father or controlling mother? Sexual abuse as a child? Peer labeling? Or mere choice and abnormal desire?

These questions have huge implications for gay rights, including marriage rights. If homosexuality is a product of nurture, i.e. it is a learned behavior, it can be changed. But if it is inborn, change is off the table and discrimination becomes a serious issue. With that in mind we will now look at what modern science has to say about the matter.  As a trained biologist, I believe I can offer some clarification and truth, and lay forth fact-based information.

“Where is the gay gene 'missing link?'” I was asked this question recently, posed by a man who believes, because no specific “gay gene” has been found, that homosexuality is therefore not biologic in its causation. But biology is not that simple, and that question shows a lot of confusion of even basic biology. Many biological traits do not result from merely one gene. Many traits are polygenic, i.e. multiple genes working in concert, determining how a trait is expressed. Examples of polygenic traits would be eye and skin color. Some scientific research indicates that sexuality may also be polygenic. It would be incredibly difficult to identify the correct combination of genes which together may cause homosexuality, due to the fact that humans have over 25,000 genes in their body.

If one single gene is not found for a given trait it does not mean that trait is not biological. The specific trait may result from the cumulative effects of varying combinations of genes. That is why no single “gay gene” has been discovered to date, and most likely never will be. 

Epigenetics is another promising area in research. Traits that are epigenetic are largely dichotomous and show up only if a cumulative genetic and pre-natal hormone target passes a threshold level. Also, homosexuality may be inborn even if it is not genetic. Not all biological traits are determined by genes. Bear in mind, for example, that women should not drink alcohol or smoke when they are pregnant because various fetal defects may result from such prenatal influences. These are non-genetic traits which are nevertheless inborn and biological. 

The neurohormonal theory is, in my opinion, the best supported and most thoroughly researched theory to date as to the most common genesis of homosexuality.

Our starting point is the human brain, the seat of essentially all that makes us human: our intellect, memory, language, emotion, creativity and imagination, our ability to dream, plan ahead, and solve problems, and of course our capacity to both love and to hate. The brain is the well-spring of it all, and on an embryologic level, everyone's brain starts out as “female;” female is essentially the default setting for every embryo. Most embryos that are chromosomal males will then be masculinized at certain developmental stages.

This is basically true but can be somewhat misleading or confusing. What is meant by this, is that it is simply impossible to tell the sex of any human embryo from the point of conception up through the first five weeks of development. In other words: humans start out as unisex. At that stage, external genitals include an undifferentiated glans area that will eventually become either the penis in a male or the clitoris in a female, and labioscrotal swellings on either side of an opening known as a urethral groove will either eventually fuse to form the scrotum in a male or remain separate and develop into the labia majora in a female.

All the changes that occur in the developing XX or XY embryo, including the internal formation of the paramesonphrenic and mesonphrenic ducts (which eventually morph into the vasa deferentia in the male embryo and the uterine tubes in the female), are mediated by numerous genes that either trigger or inhibit the release of hormones and enzymes. In males, the most important of these is testosterone. This is triggered by the SRY gene (the Sex-determining Region of the Y chromosome), which sets in motion a domino effect that causes the sex glands to differentiate into testes and start producing testosterone.

This testosterone and its converted form, dihydrotestosterone, not only “masculinizes” the embryonic and fetal anatomy, but also masculinizes its brain. For the brain, this exposure is most important during critical periods of fetal development in the second trimester. Specific areas of the brain have different critical periods, and without testosterone (or with too little or too much testosterone), or if the brain does not have the receptors to absorb appropriate levels of available androgens, the brain remains unaltered. That is to say, for example, the body may continue to develop as anatomically male, but the brain remains in its default, undifferentiated, some may say “female,” state.

The anterior hypothalamus

Now then, looking deeper inside the brain we find a small region at the base of the diencephalon known as the anterior hypothalamus. One of its jobs is to affect sexual impulses, such as romantic desires and love. Even if the rest of the brain may masculinize to greater or lesser degrees, the anterior hypothalamus has the potential to remain unaltered due to the timing of the hormonal release or a lack of androgen receptors in the region. This is incredibly significant because it, in essence, explains male homosexuality. Furthermore, if the necessary androgens are not present in sufficient amounts, an intermediary orientation may arise, explaining bisexuality. And androgens found in females may influence the development of the female brain as well. If androgens are released in significant amounts, the anterior hypothalamus may masculinize, leading to a homosexual orientation in females.

This theory is not simply the opinion of a few scientists, nor is it postulated by only one or two studies. It has been bolstered by each new study conducted, including studies on ferrets, rats, hamsters, dogs, pigs, and primates, in which testosterone levels were manipulated in the laboratory and the resulting offspring clearly exhibited homosexual behavior. To put not too fine a point on it, the neurohormonal theory is arguably the leading view on the development of homosexuality.

In 1991, Simon LeVay, a neuroscientist in California, USA, found a very important link between homosexuality and the anterior hypothalamus. He found that the nucleus of cells within the third interstitial nuclei of the anterior hypothalamus (INAH-3) markedly differs in size between heterosexual males and females. It was found that the nucleus in heterosexual males is an average of two to three times larger than it is in females. Interestingly enough, the average size of the nucleus in homosexual males is the same as in females.

Why is this significant? Because as we learned above, this region of the brain is important in regulating sexual behavior. LeVay commented that the size of the nucleus is determined by the level of circulating testosterone during a critical period of fetal development. He referenced a study on monkeys, noting that increased prenatal testosterone increased aggressive behavior in females and decreased it in males, and similar findings are shown in humans. 

Recent studies on sheep further supports these findings. Researcher Charles Roselli and his colleagues showed that roughly six to ten percent of rams exhibit an exclusive preference for other males. (Read more on gay percentages in FAQ 4 and 5.) Homosexual rams have been found to have lower levels of circulating testosterone than heterosexual rams, and examination of nucleus size in rams' hypothalami showed that the average size of the nucleus in homosexual rams was the same as in ewes, and both were considerably smaller than the average in heterosexual rams. 

The studies conducted by LeVay and Roselli give evidence that the hypothalamus, and specifically the nucleus of INAH-3 cells, could be either a direct or indirect cause of homosexuality. A concern was raised (by religious conservatives no less) that it is difficult to know whether the smaller nuclei was the cause or the effect of homosexual behavior in humans, and even LeVay himself mentions this. He notes, though, that the studies of animals indicated the size of the cell nuclei is determined during early fetal development and remains unchanged thereafter. Thus, the size of the nuclei does not appear to be affected by the behavior.

He=heterosexual, Ho=homosexual, M=men, W=women

This brings us then to pheromone studies, which give further support for the neurohormonal theory. Pheromones are chemical signals, and are important sexual stimulants in animals. Recent studies have shown they are quite significant in humans as well.

In 2005 researchers Ivanka Savic and Per Lindström in Sweden found that the anterior hypothalamus in homosexual men and heterosexual women responds almost identically to a progesterone derivative, AND, which is found in male sweat. There was no response in heterosexual males. 

When stimulated with an estrogen steroid derivative, EST, which is found in female urine, the response in homosexual males was again similar to that of heterosexual females: the anterior hypothalamus did not react to EST, although the olfactory regions did. In heterosexual males, however, the anterior hypothalamus did react to EST. Therefore, the anterior hypothalamus in both homosexual males and heterosexual females responds to a putative pheromone compound produced in much higher quantities in males than in females and does not respond to a compound produced in females.

These are biological substantiations that are separate from behavior, and do not correspond with mere “choice.”  Lead scientist and doctor Ivanka Savic went so far as to say, "There is simply too much information available that points to homosexuality not being a sexual orientation one 'develops', but something one is born with." 

Another study, conducted by Hans Berglund and his colleagues, obtained similar results in a study of homosexual females. They found that EST activates the anterior hypothalamus in heterosexual males while AND activates the olfactory regions. However, in homosexual females EST activates both the olfactory region and the anterior hypothalamus, while AND does not activate the anterior hypothalamus. The implication is that female homosexuality differs somewhat from male homosexuality.

This brings us next to intersexuals. Where do people who are neither “male” nor “female” fit into the equation? Intersex individuals are persons who have combinations of genitals and chromosomes that do not follow the majority pattern. Some intersex persons, known medically as hermaphrodites, are born with the genitals of both sexes. And this is actually not as rare as you may think. The American Journal of Human Biology reported in 2000 that approximately 1 in 100 people are born with non-standard anatomies, and 1 in 2,000 children are born with a notably ambiguous sex. Are we to assume, that because these individuals do not fit into either a biologic male or biologic female category, that they are somehow not “natural” or are not “real” humans? Obviously that would be absurd, because we cannot classify who are “real” men or “real” women based on the presence, absence, or size of external genitalia, the numbers and kinds of chromosomes a person has, sex hormone blood levels, or muscle dimensions.

Scientifically speaking, intersexuality is solidly chromosomal in its genesis. On the short arm of the Y chromosome in a developing Y sperm is where the SRY (sex-determining region of the Y chromosome) gene is typically located. Sometimes, for reasons completely out of the control of anyone, that gene moves and ends up spliced onto an X chromosome in a developing X sperm. When that gene is missing from a Y sperm that has fertilized an egg cell, the resulting XY embryo develops a feminine anatomic form. Conversely, when the gene splices onto an X sperm, the resulting XX embryo usually develops a male anatomic form. Therefore, intersexuality includes XY females and XX males, as well as persons with ambiguous internal and/or external genitalia. 

Biologist Dr. J. Pearson states that “There really is no good legal definition of gender. Certainly, one cannot define a male as someone having two testes. Does that person stop being a male if he must have a bilateral orchiectomy (both testes removed) because of cancer? Should that person no longer be considered a male? No, I think you see how ridiculous that would be. Does a woman who has had a total hysterectomy stop being female? No, from a biological standpoint, maleness or femaleness is first and foremost a state of mind.” 

Throughout the 20th century in Western countries, it was common practice for physicians to perform an operation on newborn intersex babies so that they would “fit” into traditional male or female categories. Until genetic testing was available, surgery did not always align the genitals with the individual's chromosomal pattern. Since it is much easier to fashion a vagina rather than a penis and scrotum with testes, the vast majority of these babies were shaped into and “assigned” as female. What is interesting to note, is that the majority of genetically male intersex individuals who were surgically shaped into anatomic females as neonates, nevertheless grew up to become attracted to females. Likewise, the genetic females were attracted to males, regardless of how they were assigned and raised.

This is incredibly insightful in the question of nature versus nurture. These genetically male intersex individuals were anatomically shaped into females, raised as females by their parents, complete with dresses and dolls and all things feminine, yet once they reached puberty their attraction was toward females. They then identified as lesbians, even though they were actually chromosomal heterosexual males. Their environment, peer associations, and “learned” gender identity had no bearing on their chromosomal sex and hardwired sexual orientation, which was heterosexual. This, to me, is some of the strongest evidence of nature over nurture in this debate.

There have also been incidences of this in relation to ablatio penis procedures. Rarely, a boy's penis can become damaged around the time of birth. The repair is known as ablatio penis, or removal of the organ. The child's gender is then surgically reassigned so that he appears as a female and is raised as one. There have been a few instances of this that have been studied, and those individuals have grown to find they are attracted to females (i.e. nature won, not nurture).

CAH, or congenital adrenal hyperplasia, is a naturally occurring and recessive trait that causes production of testosterone in genetic females. Masculinization of the genitals and of the brain in varying degrees is the result. The majority of CAH individuals are attracted to other females, again highlighting the importance of genetics in determining sexual orientation through the process of hormones. 

Cloacal exstrophy is another disorder of embryogenesis that causes poor differentiation of the genitals but not the brain. Genetic males are frequently raised as females because, anatomically, that is how they appear. However, the vast majority of them grow up to become attracted to females. 

An X-linked genetic mutation known as androgen insensitivity syndrome (AIS) makes genetic males insensitive to androgens (such as testosterone), so that neither their brains nor their genitals masculinize. To support the neurohormonal theory there would need to be a dramatic increase in attraction to males among AIS males when compared to other males, and low and behold, virtually all AIS males are attracted to males.

Through the course of each of these studies of intersexuals, it becomes more clearly substantiated that sexual orientation is determined in utero by both genetics and the prenatal environment, and is not the result of any learned behavior.

In light of this, Dr. Agnes Bolsø, professor of Sociology and Gender Research at the Norwegian University of Science and Technology, says, ''Attraction to persons of the same sex is 100% inborn and heritable. The inclination [...] for homosexuality is inborn and accompanies our species' biological outfitting.'' 

I will end with the words of American law professor Edward Stein, who puts it very well:

“There is also observational evidence that suggests that sexual orientations are not chosen, that is, scientific, clinical, psychological, and testimonial evidence that a person cannot change his or her sexual orientation. Countless numbers of gay men and lesbians have attempted to change their sexual orientation through one or another kind of treatment.  Attempted treatments have included lengthy psychoanalysis, prayer, hormonal injections, and electric shock treatment to name a few.  All such treatments have been dramatic failures.  

“That most people who have tried to change their sexual orientations have failed seems to count against voluntarism about sexual orientation.  Further, in places where there are no positive representations of lesbians and gay men, where homosexuals are violently repressed and severely punished, and in which social pressures push an individual to be heterosexual, there are still people who are sexually attracted to people of the same sex-gender.  It seems that at least some of these people living under such conditions would choose to be heterosexuals if they could.  Since they are not in fact heterosexuals, this suggests that they do not have a choice in the matter.”

Related posts in this blog for further information:

1. The science of "Born this way"
2. Gay sheep in hypothalamus research
3. The evolutionary multi-functionality of the human body ('complementarity' of sex organs)
4. The human brain registers love as love, regardless of sexual orientation

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