Sex and the Brain
SEXUAL DIMORPHISM
Humans are sexually dimorphic (di, “two”; morph, “type”). That is, we come in two styles. How one conceptualizes these differences depends on one’s perspective. Table 16.1 summarizes the major categories of sexual dimorphism. In this chapter, we focus on how the hormones change the morphology of the brain and how this affects the behavior and sexuality.
Pink and Blue
In general, men and women behave differently and enjoy different activities. The etiology of this difference remains a hotly debated topic. Is it nature or nurture—genetic or environmental? With humans, it is almost impossible to tease out these opposing causes. The signals a baby receives about its sexual identity start early—in the nursery. Typically, boys favor construction and transportation toys. Girls show less rough physical play and prefer toys such as dolls. Is this a product of learned gender social roles or something more innately wired in the brain?
TABLE 16.1 Different Ways of Conceptualizing Sexual Dimorphism | ||||||||||||||
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A study with vervet monkeys suggests that the choices of toys children make to play with are more ingrained than some might think. Monkeys in large cages at the University of California, Los Angeles Primate Laboratory were allowed 5 minutes of exposure to individual toys classified as “masculine” (police car and ball) or “feminine” (doll and pot). The amount of time they were in direct contact with each of the toys was recorded. Figure 16.1 shows a male and female monkey playing with the toys and the percent time that each gender spent in contact with the toys. These results show that even nonhuman primates who are not exposed to social pressure regarding toy preference will choose gender-specific toys.
If we remember the important role of pleasure in determining behavioral preferences, we can speculate that the monkeys spend more time with the toys they enjoy. Likewise, we can speculate that the association between an object and the pleasure is hardwired in the brain. Furthermore, some of this “wiring” must have arisen early in human evolution before the emergence of our hominid ancestors.
The Boy Who Was Raised as a Girl
One of the more remarkable stories of sexually dimorphic behavior involves a tragic story of a boy raised as a girl. David was 8 months old in 1966 when his entire penis was accidentally burned beyond repair during a routine circumcision. Dr. John Money, a psychologist at Johns Hopkins Hospital with expertise in sexual reassignment, convinced the family to proceed with surgical sex change and raise the boy as a girl. Dr. Money believed that sexual identity/orientation developed
after 18 months of age and children could adapt to a new sexual identity if the procedure was started early enough. David provided an ideal case study as he had an identical twin brother with a normal penis.
after 18 months of age and children could adapt to a new sexual identity if the procedure was started early enough. David provided an ideal case study as he had an identical twin brother with a normal penis.
Amazingly, Dr. Money reported in the medical literature that the reassignment was a success, but it was in actuality a disaster. David, whose name was changed to Brenda, did not want to wear dresses, or play with dolls. She preferred to play with guns and cars. She could beat up her brother and threw a ball like a boy. Worst of all, this unusual behavior was not well received at school. She was relentlessly teased for her masculine traits. Brenda was shunned by the girls and not accepted by the boys.
By the time Brenda was 14 years old she was still unaware of the sexual reassignment and remained distressed. A local psychiatrist who was treating Brenda convinced the parents to reveal the truth. Brenda recalls her reaction, “Suddenly it all made sense why I felt the way I did. I wasn’t some sort of weirdo.”
David immediately decided to revert to his genetic sex. Within several months, he began going out in public as a boy. He stopped estrogen and started testosterone. He had bilateral mastectomies and several operations to rebuild male genitalia. He eventually married in his twenties although he could not have children. However, he battled with depression and the demons from this childhood experience. In May 2005, at the age of 38, he killed himself.
The significant point about this case is that in spite of being raised as a girl and in spite of the presence of estrogen hormones and the absence of testosterone, David continued to have male pattern psychosocial and psychosexual development. Larger case studies are consistent with David’s experience. One analysis of XY individuals assigned female roles at birth due to a severe pelvic defect (cloacal exstrophy) found that all showed masculine tendencies. Slightly more than half chose to declare themselves male when older. These studies suggest that something permanent happens in utero that determines sexual identity/orientation.
Environment
It would be naive to dismiss the significance of environment on sexually stereotypical behaviors. History is replete with examples of men and women showing varying amounts of masculine and feminine behavior that are clearly molded by shifts in social norms. Kim Wallen reviewed 30 years of research with rhesus monkeys and attempted to separate hormonal and social influences. For example, rough and tumble play is one of the most robust sexually dimorphic behaviors. Juvenile males wrestle more frequently than females in almost every rearing condition. However, if reared in a group with only males, they (males or females?) actually engage in less rough play. Likewise, mounting behavior is seen more with males than females. However, when reared in isolated, same-sex environments, males display less mounting while females display more such behavior.
Rust et al. looked at gender development in preschool children and the effect of an older sibling. They discovered that having an older brother was associated with greater masculine and less feminine behavior in boys and girls. However, boys with older sisters were more feminine but not less masculine, whereas girls with older sisters were less masculine but not more feminine.
Together, these studies suggest interplay between hormones and environment. That is, biologic factors predispose individuals to engage in specific behaviors, which can be modified by social experience.
GONADS
The gonads (ovaries and testes) serve two major functions. First, they produce eggs or sperm to pass on DNA to the next generation. Second, they produce the sex hormones that not only promote the development of secondary sexual characteristics but also drive the behavior that increases the chances of an egg and sperm meeting.
HORMONES
Figure 14.8 shows the classic experiment by Berthold who was the first to establish that the testes contain a substance that controls the development of male secondary sexual characteristics. In Chapter 7, we discussed the relationship between the cortex, hypothalamus, pituitary gland, and end organ. Briefly, with input from the cortex, the hypothalamus produces gonadotropin-releasing hormone (GnRH), which in turn stimulates the anterior pituitary gland to produce luteinizing hormone (LH) and follicle-stimulating hormone (FSH). LH and FSH stimulate the gonads to produce the sex hormones.
Cholesterol is the precursor of all steroid hormones. Figure 7.7 shows the three major steroids synthesized from cholesterol: glucocorticoids, mineralocorticoids, and the sex steroids. The sex steroids are synthesized in the adrenals or gonads. Because the steroid hormones are lipid soluble and easily pass through the cell walls, they are released as they are synthesized.
Testosterone, as shown in Figure 16.2, is converted into 17-β-estradiol (E2) and an androgen, 5-α-dihydrotestosterone (DHT). (An androgen is a generic term for a hormone that stimulates or maintains male characteristics.) Amazingly, much of the androgen effects in the brain are actually implemented by 17-β-estradiol. For example, an injection of estrogen to a newborn rat is more masculinizing than an injection of testosterone.
Why do the maternal estrogens not masculinize all fetuses? One of the functions of α-fetoprotein during pregnancy is to bind with maternal estrogens, which are then cleared through the placenta. This protein, which does not bind testosterone effectively, prevents estrogens from reaching the brain.
We have discussed in other chapters how the sex steroids can work directly on synaptic receptors or indirectly through gene transcription (see Figures 5.3, 7.1, and 7.3). These different effects are summarized in Figure 16.3. The direct effects are fast, while the indirect effects take longer to transpire. Because the sex hormones can influence neural function, they are sometimes called neurosteroids in neuroscience literature.
![]() FIGURE 16.2 • The sex hormones are synthesized from cholesterol. Testosterone serves as a prohormone for 17-β-estradiol. |
Differentiation and Activation
The development of sexual dimorphism is dependent on the sex hormones. The presence of testosterone at critical periods of time both masculinizes and defeminizes the brain. Likewise, the absence of testosterone feminizes and demasculinizes the brain. In 1959 William C. Young et al. published a classic paper that rivals Berthold’s work with roosters in helping us to understand the fundamental principles of hormones and behavior.
To understand Young’s study it is important to be aware of the different sexual postures males and females display at appropriate times.
Female rodents will stand immobile and arch their backs: lordosis. Males will mount such a receptive female. Females and males rarely (although not completely) exhibit the opposite behavior. Researchers use the presence or absence of lordosis and mounting as expressions of sexual behavior. For example, castration of a male stops his mounting behavior. But this can be reinstated with injections of testosterone.
Female rodents will stand immobile and arch their backs: lordosis. Males will mount such a receptive female. Females and males rarely (although not completely) exhibit the opposite behavior. Researchers use the presence or absence of lordosis and mounting as expressions of sexual behavior. For example, castration of a male stops his mounting behavior. But this can be reinstated with injections of testosterone.
Young’s group sought to understand the effects of early and late exposure to sex hormones on sexual behavior. Their experiment, which is shown in Figure 16.4, started with injecting testosterone in a pregnant female guinea pig. Their first observation (not shown in the figure) was that female pups exposed to high doses of androgens in utero were born with masculinized external genitalia.
The rest of the study focused on the female pups, which were allowed to mature and were then spayed. Later, they were all given estrogen and progesterone to stimulate female sexual behavior. Each was paired with a normal male guinea pig. Sometime later, the procedure was reversed. All were injected with testosterone and paired with a receptive female. The results were striking. The females exposed to testosterone in utero failed to display lordosis when given estrogen and progesterone. However, they would mount other females when given testosterone. The control group displayed the opposite behavior.
This elegant experiment established a clear distinction between the differentiating effects of sex hormones during development and the activating effects during adulthood. The females exposed to testosterone in utero had alterations in the organization of their brains that prevented the normal activation by female sex hormones as an adult.
Human Congenital Anomalies
Occasionally, people are born with genetic alterations that give us insight into the differentiation and activation of human sexual dimorphism. One such condition is congenital adrenal hyperplasia. Children with this condition are exposed to excessive androgens due to overactive fetal adrenal glands. Paradoxically, the condition is caused by an impaired ability of the fetal adrenal gland to produce cortisol. Because the pituitary fails to receive the appropriate negative feedback, it continues to secrete adrenocorticotropic hormone (ACTH), which in turn induces hyperplasia of the androgen-producing cells of the adrenal cortex.
![]() FIGURE 16.4 • Guinea pigs exposed to testosterone in utero (A) fail to show feminine sexual behavior (B) when given female sex hormones and instead act like males (C) when given testosterone. |
As we might predict from Young’s studies with guinea pigs, human males are unaffected by the exposure to excess adrenal androgens in utero. Females, on the other hand, are born with masculinized external genitalia. Additionally, the females tend to exhibit more rough and tumble play as children. As adults, they have an increased tendency to prefer other females as partners.
An extraordinary condition in men provides a different example of anomalous sexual development. Androgen insensitivity syndrome (AIS) is a condition in which XY (male) individuals are born as normal appearing females. The problem is caused by a mutation in the androgen receptor. These individuals produce testosterone, but the cells are unable to recognize it. Consequently, there is no activation of the genes necessary for male characteristics.
These individuals are born looking like normal little girls and are raised as such (Figure 16.5). Typically, the problem is only recognized when they fail to menstruate in adolescence. Unfortunately, they are unable to conceive as they have failed to develop uteri, fallopian tubes, and ovaries.
However, their behavior is unequivocally feminine. Hines et al. examined the psychological development of 22 XY individuals with complete AIS compared with 22 XX normal controls and found no differences on any measure of psychological outcome. They concluded that these results argue against the need for ovaries and two X chromosomes in the development of traditional feminine behavior. Likewise, it reinforces the importance of the androgen receptor in masculine development. It is an interesting thought that all humans (both men and women) would develop into women unless other hormones intervene. The default model for mankind is a woman!
However, their behavior is unequivocally feminine. Hines et al. examined the psychological development of 22 XY individuals with complete AIS compared with 22 XX normal controls and found no differences on any measure of psychological outcome. They concluded that these results argue against the need for ovaries and two X chromosomes in the development of traditional feminine behavior. Likewise, it reinforces the importance of the androgen receptor in masculine development. It is an interesting thought that all humans (both men and women) would develop into women unless other hormones intervene. The default model for mankind is a woman!

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