Brain Aromatase: Dyed-in-the-Wool Homosexuality

“Tell me where is fancy bred, or in the heart or in the head?”—William Shakespeare, The Merchant of Venice, Act III, Scene 2 Today’s neuroscientist has no hesitation answering Shakespeare’s question taken literally: of course love and desire are generated in the brain, that heady organ in charge of all our thoughts and feelings. Therefore, it must be the brain that is responsible for most men being sexually attracted to women and for most women being sexually attracted to men. Starting in 1985, several structural sex differences were described in the human brain (1), including the third interstitial nucleus of the anterior hypothalamus (INAH3), which has a greater volume in men than in women (2). But there was no way to know which, if any, of these neural sexual dimorphisms were responsible for the robust human sex difference in sexual partner preference. Then in 1991, Simon LeVay (3) not only replicated the sex difference in human INAH3 but reported that the nucleus in homosexual men was indistinguishable from that of women, i.e. significantly smaller than in heterosexual men. Suddenly it became plausible to think that possessing a large INAH3 might cause a person to be attracted to women, whereas having a small INAH3 might cause a person to be attracted to men. In this issue, Charles Roselli et al. (4) describe a sexually dimorphic hypothalamic nucleus in sheep, another mammalian species in which a minority of males display a lasting preference for mating with males rather than with females. Furthermore, they find that those rams that prefer mounting males have a smaller nucleus in this brain region than do rams that prefer mounting ewes. These observations lend strong support to the idea that the structure of the anterior hypothalamus in mammals influences sexual orientation in males. To understand the context of this finding, we first have to deal with some confusing issues of terminology. The region of the anterior hypothalamus known as the preoptic area (POA) has long been implicated in male sexual behavior. Lesions of this region in males, across a wide variety of vertebrate species, cause the animals to lose interest in mating with females (5). So it was perfectly reasonable for Roger Gorski and colleagues (6) to look for sexual dimorphisms in the rat POA, and they struck gold. Within the POA was a subregion that in Nissl stain is five to six times greater in volume in male rats than in females. Impressed by the findings in rats, Dick Swaab and Eric Fliers (1) of The Netherlands Institute for Brain Research found a nucleus in the POA of humans that was larger in men than in women, so they named it the sexually dimorphic nucleus (SDN)-POA. Unfortunately, when Gorski’s group examined the human POA, they were unable to decide which of the several nuclei there were homologous to the rat SDN-POA. So they named the four neuron groups the INAH and numbered them, starting with the group Swaab and Fliers termed the SDN-POA ( INAH1). Gorski’s group found that INAH3 was larger in men than in women (2), a finding that LeVay would later replicate. Unfortunately, neither Gorski’s group nor LeVay found a sexual dimorphism in INAH1, failing to replicate Swaab and Fliers’ findings, which may represent a matter of statistical power, because the Dutch group have much larger sample sizes (7). Given this complicated nomenclature, the Roselli group decided to call the nucleus in the sheep POA the ovine SDN (oSDN). This title represents a strictly descriptive name (it’s larger in males than in females), without taking a stand on whether it is homologous with the rat SDN-POA and/or the human INAH3. That’s a wise decision because there is no sure way to determine whether any of these nuclei are homologous across species. So we cannot be sure that the oSDN is homologous with the human INAH3, but they are definitely in roughly the same part of the brain. Plus in both species, the nuclei are smaller in those minority of males that are sexually attracted to other males, which certainly suggests that the two nuclei (homologous or not) are involved in sexual attraction in male mammals. Of course, Shakespeare was also posing a deeper question. Do we hit upon the object of our affection through carefully considered, rational analysis of the sort we might use in selecting tires for an automobile, or through emotional reactions, which are often so difficult to understand, far less to explain to others? Most people, even scientists, would agree that sexual attraction is more a matter of emotion than intellectual reflection if for no other reason than because it often seems so arbitrary. Before you object that surely there is a continuum of attractiveness, remember that the vast majority of people are attracted exclusively to people of the opposite sex, and find same-sex individuals completely unacceptable as potential mates. This dichotomy of desire is so pervasive in our culture, so automatic in our response to other people, that it’s easy to overlook how truly strange it is. How can half the population regard Brad Pitt as dreamy, whereas the other half feels absolutely no attraction to him at all? How did each of us come to be so finicky that we find billions of people totally unworthy as sexual partners? And does this selectivity result from a choice made during childhood? “Let’s see, I’ll have gym at school today, so I’ll wear white socks and tennis shoes. Gosh, as long as I’m making decisions I guess I better be attracted to girls for the rest of my life, too.” If we don’t use our head to decide which gender to lust after, maybe the decision is made somewhere even further down than our heart. Neuroendocrinologists’ work on nonhuman animals offers a theory that the gonads play a role in sexual orientation. In mammalian models, a testicular hormonal signal—androgen—masculinizes the developing genAbbreviations: INAH, Interstitial nucleus of the anterior hypothalamus; oSDN, ovine SDN; POA, preoptic area; SDN, sexually dimorphic nucleus.