Women born with a rare condition that gives them a Y chromosome don't only look like women physically, they also have the same brain responses to visual sexual stimuli, a new study shows.
The journal Hormones and Behavior published the results of the first brain imaging study of women with complete androgen insensitivity, or CAIS, led by psychologists at Emory.
"Our findings clearly rule out a direct effect of the Y chromosome in producing masculine patterns of response," says Kim Wallen, an Emory professor of psychology and behavioral neuroendocrinology. "It's further evidence that we need to revamp our thinking about what we mean by 'man' and 'woman.'"
Wallen conducted the research with Stephan Hamann, Emory professor of psychology, and graduate students in their labs. Researchers from Pennsylvania State University and Indiana University also contributed to the study.
The Y chromosome was identified as the sex-determining chromosome in 1905. Females normally have an XX chromosome pair and males have an XY chromosome pair.
By the 1920s, biochemists also began intensively studying androgens and estrogens, chemical substances commonly referred to as "sex hormones." During pregnancy, the presence of a Y chromosome leads the fetus to produce testes. The testes then secrete androgens that stimulate the formation of a penis, scrotum and other male characteristics.
Women with CAIS are born with an XY chromosome pair. Because of the Y chromosome, the women have testes that remain hidden within their groins but they lack neural receptors for androgens so they cannot respond to the androgens that their testes produce. They can, however, respond to the estrogens that their testes produce so they develop physically as women and undergo a feminizing puberty. Since they do not have ovaries or a uterus and do not menstruate they cannot have children.
"Women with CAIS have androgen floating around in their brains but no receptors for it to connect to," Wallen says. "Essentially, they have this default female pattern and it's as though they were never exposed to androgen at all."
Wallen and Hamann are focused on teasing out neural differences between men and women. In a 2004 study, they used functional magnetic resonance imaging (fMRI) to study the neural activity of typical men and typical women while they were viewing photos of people engaged in sexual activity.
The patterns were distinctively clear, Hamann says. "Men showed a lot more activity than women in two areas of the brain -- the amygdala, which is involved in emotion and motivation, and the hypothalamus which is involved in regulations of hormones and possibly sexual behavior."
For the most recent study, the researchers repeated the experiment while also including 13 women with CAIS in addition to women without CAIS and men.
"We didn't find any difference between the neural responses of women with CAIS and typical women, although they were both very different from those of the men in the study," Hamann says. "This result supports the theory that androgen is the key to a masculine response. And it further confirms that women with CAIS are typical women psychologically, as well as their physical phenotype, despite having a Y chromosome."
A limitation of the study is that it did not measure environmental effects on women with CAIS. "These women look the same as other women," Wallen explains. "They're reared as girls and they're treated as girls, so their whole developmental experience is feminized. We can't rule out that experience as a factor in their brain responses."
The findings may have broader applications in cognition and health. "Anything that we can learn about sex differences in the brain," Wallen says, "may help answer important questions such as why autism is more common in males and depression more common in females."

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