The Neuroanatomy of Homosexuality


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Homo

By Claire Bryson

The anterior hypothalamus of the human brain is sexually dimorphic and has been investigated for dimorphism with regards to sexual orientation through examination of postmortem brains of homosexual males, heterosexual males, and heterosexual females. Studies examining the interstitial nuclei of the anterior hypothalamus3 and the anterior commisure4 have shown correlation to sexually-orientated dimorphism. Through further research, a relationship between the development of these sexually dimorphic regions and steroid hormone levels has been established.  Though neither consequence nor causation can be definitively demonstrated from this research, its implications are suggestive of the early differentiation of human sexual orientation and its origins spanning neurobiology and endocrinology.>

Sexual orientation has long been a topic of controversy and debate in social, political, and scientific circles. In the last twenty years, scientific efforts have examined the biology of this phenomenon. Most of this research has focused on the anterior hypothalamus  and the preoptic area (POA) within the larger hypothalamic region. Historically, these areas have shown a relationship to male sexual behavior.1 More recent research has elucidated differences in the anterior hypothalamus and its endocrinological functions between heterosexual males and homosexual males. In the current literature, there is little doubt that these areas of the brain are sexually dimorphic; however, debate still exists regarding how these  differences affect sexual orientation.

To understand male sexual orientation as a phenomenon, familiarity with the development of male fetuses must be discussed. Gender is determined by the activity of a lone pair of sex chromosomes passed on by the parents. Initially, the gonads are indistinct and can develop as either testes or ovaries. In males, the testis determination factor (TDF) gene, when expressed properly, causes testicles to develop, while in absence of its function, ovaries will develop.2 After this stage, the testes and their specific hormonal secretions direct the organization of the rest of the body, including the brain, which also develops either masculine or feminine traits. As seen from the process, humans begin as “female,” so to speak, and develop the male characteristics. Thus, hormonal secretions are both important and delicate in male development, depending largely on the androgenic, or masculinizing, steroid hormone testosterone.2 This molecule functions as a “pro-hormone” to masculinize the brain during development.2 Studies examine the occurence of this neuronal patterning according to gender and its prevalence in homosexual men in attempts to determine whether sexually dimorphic areas of the brain are affected by, or even correlate to, the sexual orientation of males.

In a key article, Simon LeVay presented the difference in hypothalamic structure between heterosexual and homosexual men3. Cited by a majority of articles in the field, LeVay’s hypothesis and study was expository and led to extensive additional research. LeVay argued that the hypothalamus held the the key to sexual orientation. He cited that, in male monkeys, lesions in this region impair heterosexual behavior without eliminating sexual drive3. LeVay investigated two specific small groups of neurons, the interstitial nuclei of the anterior hypothalamus 2 and 3 (INAH 2 and 3). He hypothesized that one or both of these nuclei would exhibit size dimorphism with sexual orientation, not just with gender as had been previously examined3. Because INAH had already been observed to be more than twice as large in heterosexual men than women, LeVay extrapolated that INAH 2 and/or 3 would be large in individuals sexually oriented towards women (heterosexual men and homosexual women) and small in individuals sexually oriented towards men (heterosexual women and homosexual men). Because brains of homosexual women were not available, only the brains of homosexual men were examined. And although most of the homosexual male samples were from post mortem AIDS patients, this had no effect on the results; comparison of heterosexual men who died of AIDS with homosexual men who died of AIDS still showed the difference in INAH3 nuclei. Furthermore, the variance of subjects by age was eliminated by age-matching study groups.

LeVay’s research found that INAH 3 did exhibit the hypothesized sexually-oriented dimorphism3. In accordance with his hypothesis, the volume of the nucleus was more than twice as large in heterosexual males as in homosexual males, a statistically significant result3. Given the double blind-procedure, no bias could exist, and no statistical difference was found when comparing brains of heterosexual males who died from AIDS to other brains of heterosexual males. Ultimately, homosexual men and heterosexual women both had smaller volumes of  INAH 3 compared to that of heterosexual men, supporting LeVay’s arguments on the nature of INAH 33.

The applications of this discovery are limited by the inability to determine causation. Because of the postmortem nature of the experiment, it was impossible to gain detailed insight into all subjects’ sexualities. This limits the ability to show correlation between brain structure and the diversity of sexual behavior. Additonally, “exceptions” to the rules do exist; homosexual males with INAH 3 regions sized appropriately to heterosexual males were observed, suggesting that INAH 3 alone does not necessarily affect sexuality. Clearly, there are further unidentified variables which impede the ability to identify the dimorphism of INAH 3 as cause or consequence of sexual orientation. Regardless, sexual orientation has a demonstrated biological correlation to some extent, which necessitates further in-depth research.

Laura S. Allen and Roger A. Gorski studied sexual dimorphism in the anterior commisure (AC) of the human brain,  a fiber bundle that is sexually dimorphic but not directly related to reproductive function4. Their study, similar to LeVay’s, examined volumetric differences between homosexual males and heterosexuals of both genders and used age-matching and double-blind procedures to elminate variance and bias4.  The AC in homosexual men was found to be 34% larger on average than that of heterosexual men and 18% larger than that of  heterosexual women4. When adjusted for individual brain mass, the AC of homosexual men was 36% larger than heterosexual men and 5.9% greater than heterosexual women. heterosexual women had an AC 28.4% greater than heterosexual males4.

The functional significance of the size of the AC is unknown, but it  shows clear sexual dimorphism and experimentally determined sexual-orientation dimorphism, similar to the INAH 3 area. Little research has examined  these differences in humans, but studies on animals have shown that they arise in the perinatal organism2. Given the results regarding both INAH 3 and AC correlation to sexual orientation, the understanding that no single brain structure correlates to sexual orientation carries weight. The apparent interconnected nature of varying brain regions suggests that factors operating early in development differentiate on the basis of  gender and sexual orientation within sexually dimorphic structures and brain function in a cumulative manner2. Exploring which specific factors influence which kind of development requires an endocrinologic approach alongside traditional neurobiological studies.

The endocrinologic approach examines the role of sex hormones in sexual orientation. In mammalian models, like in humans, an androgen masculinizes the developing genitalia and then the brain as well1. The question is whether or not these fetal androgens alone also ‘masculinize’ the brain or if there are further key players in development such as neurotransmitters or neurodevelopmental factors.

Conflicting studies have suggested that boys may turn out homosexual as a result of lower-than-normal fetal androgen, from higher-than-normal levels, or for reasons having nothing to do with androgens, with no study appearing more conclusive than the rest1. However, through studies of sheep, Roselli et al.5 have some evidence that male-oriented rams receive lower-than-normal androgen stimulation of the brain. Since testing in rats has suggested that estrogen may affect the volume of the ovine sexually dimorphic nucleus (oSDN), this effect was then studied in rams to explain the minority of males which display a preference for mating with other males over females5. It was found that male-oriented rams did in fact have a smaller nucleus in this brain region than female-oriented rams5. These observations lend strong support to the importance of the anterior hypothalamus’s influence on sexual orientation in males5.  The enzyme aromatase converts androgens like testosterone into estrogens and plays a crucial role in the masculine development of the rat SDN-POA, masculinizing the rat brain and leading to masculine behavior1. These results show a relationship between steroid hormones, oSDN morphology, and the resulting sexual orientation in rams. With such progress using with rams as a mammalian model, researchers may be able to draw implications about human sexual orientation.

Before being applied to humans, research must determine more precisely how steroid hormones and the related biology affect the size of the oSDN. Does the level of aromatase activity determine oSDN size, or does oSDN size determine the level of aromatase? If aromatase effects in the POA are responsible for the size of the oSDN and the size of the oSDN is in turn responsible for sexual preference, then interfering with hypothalamic aromatase in developing rams may reliably shrink the oSDN and produce male-oriented rams5. This demonstration would be suggestive of a causal relationship between steroid action, hypothalamic morphology, and sexual preference in sheep5. By extension, this demonstration could also suggest that steroid hormones affect the human hypothalamus to influence sexual orientation. Studies investigating this effect would further emphasize the critical biology of sexual orientation and eliminate the social argument of “choosing” one’s sexuality.

There is still significant research that needs to be done before anything truly conclusive can be reached. First of all, these studies lack homosexual female subjects. Due to the prevalence of AIDS among the homosexual male community, records of sexual orientation allow for postmortem analysis of their brains. This is not the case for homosexual women, as a population that has  not been as affected by AIDS. A longitudinal study would be required to track homosexual women to ultimately allow for post mortem analysis on the sexually dimorphic nucleus areas of the hypothalamus. Longitudinal studies could also examine varying levels of steroid hormones throughout development. There has been speculation that homosexual men in general have a lower age at puberty, perhaps due to variations in hormone levels6. In general, future research could also focus on the relationship between steroid hormones and development of the SDN in the hypothalamus. Related topics of study remain largely unexplored in humans, such as the preliminary studies of pheromone sensitivity based on individual’s sexual orientation 7.

The question of human bisexuality remains. What biological evidence could be shown in such an individual? It could prove enlightening to thoroughly examine the brain of a bisexual person and find differences from both homosexual and heterosexual individuals. Still, correlating neurobiological and endocrinological dimorphism cannot argue causation without further experimentation in animal models. Additionally, separating environmental influences like factors during gestation from purely genetic ones may not be possible.  Therefore, the interaction and communication between  various fields of research on this topic will be critical to future success. A concerted effort between disparate methodologies of investigation may provide the key for advances in the years to come, and, regardless of their results, the research itself will no doubt have profound implications in society.

1. Morris, J. A., Gobrogge, K. L., Jordan, C. L. & Breedlove, S. M. 2004. Brain aromatase: dyed-in-the-wool homosexuality, Endocrinology 145:475–477.

2. Breedlove, SM. 1992. Sexually dimorphism in the vertebrate nervous system, The Journal of Neuroscience 12: 4133-4142.

3. Levay, S. 1991. A Difference in Hypothalamic Structure between Heterosexual and Homosexual Men, Science 253:1034-1037.

4. Allen LS, Gorski RA. 1992. Sexual orientation and size of the anterior commissure in the human brain, Proc Natl Acad Sci USA 89:7199–7202.

5. Roselli CE, Larkin K, Resko JA, Stellflug JN, Stormshak F. 2004. The volume of a sexually dimorphic nucleus in the ovine medial preoptic area/anterior hypothalamus varies with sexual partner preference. Endocrinology 145:478-483

6. James, W. H. 2005. Biological and psychological determinants of male and female human sexual orientation, Journal of Biosocial Science 37:555–567.

7. Savic, H. Berglund and P. Lindstrom. 2005. Brain response to putative pheromones in homosexual men, Proc. Natl. Acad. Sci. USA 102:7356–7361.

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