by : Simon LeVay and Dean H. Hamer
Researchers have long sought within the human brain some manifestation of the most obvious classes into which we are divided male and female. Such sex differentiation of the brain's structure, called sexual dimorphism, proved hard to establish. On average, a man's brain has a slightly larger size that goes along with his larger body; other than that, casual inspection does not reveal any obvious dissimilarity between the sexes. Even under a microscope, the architecture of men's and women's brains is very similar. Not surprisingly, the first significant observations of sexual dimorphism were made in laboratory animals.
Of particular importance is a study of rats conducted by Roger A. Gorski of the University of California at Los Angeles. In 1978 Gorski was inspecting the rat's hypothalamus, a region at the base of its brain that is involved in instinctive behaviors and the regulation of metabolism. He found that one group of cells near the front of the hypothalamus is several times larger in male than in female rats. Although this cell group is very small, less than a millimeter across even in males, the difference between the sexes is quite visible in appropriately stained slices of tissue, even without the aid of a microscope.
Gorski's finding was especially interesting because the general region of the hypothalamus in which this cell group occurs, known as the medial preoptic area, has been implicated in the generation of sexual behavior in particular, behaviors typically displayed by males. For example, male monkeys with damaged medial preoptic areas are apparently indifferent to sex with female monkeys, and electrical stimulation of this region can make an inactive male monkey approach and mount a female. It should be said, however, that we have yet to find in monkeys a cell group analogous to the sexually dimorphic one occurring in rats.
Nor is the exact function of the rat's sexually dimorphic cell group known. What is known, from a study by Gorski and his co-workers, is that androgens typical male hormones play a key role in bringing about the dimorphism during development. Neurons within the cell group are rich in receptors for sex hormones, both for androgens testosterone is the main representative and for female hormones known as estrogens. Although male and female rats initially have about the same numbers of neurons in the medial preoptic area, a surge of testosterone secreted by the testes of male fetuses around the time of birth acts to stabilize their neuronal population. In females the lack of such a surge allows many neurons in this cell group to die, leading to the typically smaller structure. Interestingly, it is only for a few days before and after birth that the medial preoptic neurons are sensitive to androgen; removing andoes not cause the neurons to die.
Gorski and his colleagues at U.C.L.A., especially his student Laura S. Allen, have also found dimorphic structures in the human brain. A cell group named INAH3 (derived from 'third interstitial nucleus of the anterior hypothalamus') in the medial preoptic region of the hypothalamus is about three times larger in men than in women. (Notably, however, size varies considerably even within one sex.)
In 1990 one of us (LeVay) decided to check whether INAH3 or some other cell group in the medial preoptic area varies in size with sexual orientation as well as with sex. This hypothesis was something of a long shot, given the prevailing notion that sexual orientation is a 'high-level' aspect of personality molded by environment and culture. Information from such elevated sources is thought to be processed primarily by the cerebral cortex and not by 'lower' centers such as the hypothalamus.
LeVay examined the hypothalamus in autopsy specimens from 19 homosexual men, all of whom had died of complications of AIDS, and 16 heterosexual men, six of whom had also died of AIDS. (The sexual orientation of those who had died of non-AIDS causes was not determined. But assuming a distribution similar to that of the general populace, no more than one or two of them were likely to have been gay.) LeVay also included specimens from six women whose sexual orientation was unknown.
Like Allen and Gorski, LeVay observed that INAH3 was more than twice as large in the men as in the women. But INAH3 was also between two and three times larger in the straight men than in the gay men. In some gay men, as in the example shown at the top of the opposite page, the cell group was altogether absent. Statistical analysis indicated that the probability of this result's being attributed to chance was about one in 1,000. In fact, there was no significant difference between volumes of INAH3 in the gay men and in the women. So the investigation suggested a dimorphism related to male sexual orientation about as great as that related to sex.
A primary concern in such a study is whether the observed structural differences are caused by some variable other than the one of interest. A major suspect here was AIDS. The AIDS virus itself, as well as other infectious agents that take advantage of a weakened immune system, can cause serious damage to brain cells. Was this the reason for the small size of INAH3 in the gay men, all of whom had died of AIDS?
Several lines of evidence indicate otherwise. First, the heterosexual men who died of AIDS had INAH3 volumes no different from those who died of other causes. Second, the AIDS victims with small INAH3s did not have case histories distinct from those with large INAH3s; for instance, they had not been ill longer before they died. Third, the other three cell groups in the medial preoptic areaÑINAH1, INAH2 and INAH4, turned out to be no smaller in the AIDS victims. If the disease were having a nonspeciÞc destructive effect, one would have suspected otherwise. Finally, after completing the main study, LeVay obtained the hypothalamus of one gay man who had died of non-AIDS causes. This specimen, processed 'blind' along with several specimens from heterosexual men of similar age, confirmed the main study: the volume of INAH3 in the gay man was less than half that of INAH3 in the heterosexual men.
One other feature in brains that is related to sexual orientation has been reported by Allen and Gorski. They found that the anterior commissure, a bundle of Þbers running across the midline of the brain, is smallest in heterosexual men, larger in women and largest in gay men. After correcting for overall brain size, the anterior commissure in women and in gay men were comparable in size.
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