Excerpted from Touching a Nerve: The Self as Brain, by Patricia S. Churchland. Copyright © 2013 Patricia S. Churchland. With permission of the publisher, W. W. Norton & Co., Inc.
Diverging Paths in Human Sexual Development
The basic account of a typical brain-hormone interaction for XX and XY fetuses has been outlined. But not all cases conform to the prototype. Variability is always a part of biology. For example, unusual chromosome arrangements can occur. Rarely, an egg or a sperm might actually carry more than one chromosome, so the conceptus ends up with more than just a pair of sex chromosomes. About 1 in 650 males are born with XXY, a condition known as Klinefelter’s syndrome (as I mentioned in Chapter 1, my brother has this condition). The outcome can be quite variable, but basically what happens is that the testosterone supply dependent on the Y chromosome gets swamped by the estrogen production linked to the two X chromosomes. This affects gonad development, musculature, and fertility. There are cognitive costs, too, mainly having to do with the role of the prefrontal cortex in impulse control and the capacity to delay gratification.
Other chromosomal variations are also seen: XYY occurs in about 1 in 1,000 male births. It frequently goes unnoticed because there are no consistent symptoms. At one time it was claimed, mainly on a priori grounds, that XYY persons are especially aggressive, but this turns out not to be correct. XXYY, which is much more rare (about 1 in 20,000 male births), has many deleterious effects. This condition is linked to seizures, autism, and developmental delays in intellectual functions. In about 1 in 5,000 cases, a fetus may have only a single chromosome—an X—a condition known as Turner’s syndrome. The damaging effects are very broad, including short stature, low-set ears, heart defects, nonworking ovaries, and learning deficits. If a conceptus has only a single chromosome—a Y—it probably fails to implant in the uterus and never develops.
So just at the level of the chromosomes, we see variability that belies the idea that we are all either XX or XY. What about variability in the genes that leads to variability in brain development? Various factors, both genetic and environmental, can deflect the intricate development of a body and its brain from its typical course.
Consider an XY fetus. For the androgens (testosterone and dihydrotestosterone) to do their work in its brain, they must bind to special receptors tailored specially for androgens. The androgens fit into the receptors like a key into a lock. The receptors are actually proteins, made by genes. Even small variations in the gene (SRY) involved in making androgen receptors can lead to a hitch. And small variations in that gene are not uncommon. In some genetic variants, the receptor lacks the right shape to allow the androgens to bind to it. This prevents the process of masculinizing the gonads and the brain. In other genetic variants, no receptor proteins are produced at all, so the androgen has nothing to bind to. In these conditions, the androgens cannot masculinize the brain or the body, despite the XY genetic makeup. In consequence, the baby, though a genetic male, will probably have a small vagina and will be believed to be female when born. This baby will grow breasts at puberty, though she/he will not menstruate and has no ovaries. This is sometimes described in the following way: the person is genetically a male, but bodily (phenotypically) a female. These individuals usually lead quite normal lives and may be sexually attracted to men or to women or in some cases to both.
If an XX fetus is exposed to high testosterone levels in the womb, her gonads at birth may be rather ambiguous, with a large clitoris or a small penis. This condition is known as congenital adrenal hyperplasia, or CAH. This usually results from a genetic abnormality that causes the adrenal glands to produce extra androgens. As a child, she may be more likely to engage in rough-and-tumble play and to eschew more typical girl games such as “playing house.” When at puberty there is a surge of testosterone, she may develop a normal penis, testicles will descend, and her musculature may become more masculine. Though raised as a girl, persons with this history tend to live as heterosexual males. A male XY fetus may also carry the genetic defect, but in that case, the extra androgens are consistent with the male body and brain, and the condition may go unrecognized.