Biopsychology of Sex Behavior

1. Biopsychology of Sex Behavior Lecture 3: The Sexual Brain LeVay, Ch. 10-13

2. Chapter 10 • Neural tube is a structure that gives rise to the brain and spinal cord • Fluid-filled space inside the tube becomes the system of ventricles • The cells forming inner lining of tube divide repeatedly and their daughter sides migrate outward and become part of nuclear or cortical structures (gray matter)

3. Chapter 10 • Hypothalamus arises from cells lining third ventricle • Sexually dimorphic nucleus (SDN) of medial preoptic area (MPOA) in rats is sexually dimorphic; larger in males than in females • Gorski et al.: administration of 3H-thymidine on day 18 of gestation (about 5 days before birth) permanently labeled many cells in SDN-MPOA in both sexes • During critical period (about 3 days before and 6 days after birth) cells in female died; leaving more cells in males than in females • Probably effect of hormones on neurons, which have androgen receptors; not entirely clear whether testosterone acts directly or indirectly to masculinize this nucleus • If a male pup’s testes are removed, number of cells in this nucleus decline as they do in female; injection of testosterone into the MPOA of females can partially reverse the dying off

4. Chapter 10 • Effects of hormones • Organizational: hormones influence the brain (and body) during critical developmental periods; this permanently influences the organization of the brain and other areas and affects behavior later on in life (e.g., masculinization of SDN-MPOA by testosterone during critical period) • Activational: hormones act on preexisting brain circuits and facilitate the expression of behaviors and other hormone-dependent activities; activational effects in adulthood elicit whichever pattern was organized earlier (e.g., hormones facilitate expression of male sexual behavior in adults by acting on neurons in the MPOA, which were masculinized during critical developmental period)

5. Chapter 10 • Example of organizational effects (play behavior): • Young male monkeys participate in more rough-and-tumble play than do females • This sexual dimorphism results from differences in androgen levels during prenatal development • Goy et al.: females exposed to high levels of androgens during prenatal development lead to an increase in rough-and-tumble play in young females; males whose testosterone levels were lowered during prenatal development participated in less rough-and-tumble play • Similar effect may occur in humans: girls with congenital adrenal hyperplasia (a condition caused by faulty adrenal glands that produce excessive amounts of androgens) showed male-typical play behaviors (e.g., preferred trucks over dolls)

6. Chapter 10 • Some females engage in male-typical behaviors (e.g., female rats may mount other receptive females) • Clemens: readiness of a female rat to display these male-typical behaviors is influenced by its position in the uterus when it was a fetus • Females that happened to lie between two male fetuses are more likely to display male-typical behaviors as adults than females that lie between female fetuses • It appears that testosterone from adjacent males masculinizes these females; in fact, females situated between males have higher blood levels of androgens than those situated between female fetuses • Crucial factor is presence of male fetus on the side of the female between her and the cervix—blood flows upstream, from cervix to ovary • In addition, masculinization of the external genitalia occurs in some females that are situated between male fetuses; these females are also masculinized in other behaviors as well

7. Intrauterine position effects • In pregnant rats, uterine blood flows predominantly in the caudal to distal direction (i.e. from the cervix to the ovaries) • Fetuses located distally to male pups will thus be subjected to higher levels of testosterone and fetuses located caudally to male pups will not be subjected to high testosterone levels Ryan, B. C., & Vandenbergh, J. G. (2002). Neuroscience & Biobehavioral Reviews, 26 (6), 665-678

8. Chapter 10 • Example of organizational effects (sexual behavior): • Male rat pups that are castrated at or prior to birth fail to show male-typical behaviors in adulthood (even if they are given testosterone in adulthood); interestingly, if this males are given estrogen & progesterone in adulthood, they will display lordosis when paired with a male • If castration is performed after birth, neither of these effects occur; in fact, testosterone treatment in adulthood induces male-typical sexual behaviors in these animals, while estrogen and progesterone treatments fail to induce female-typical behaviors; this would suggest that the brain was masculinized during critical period • If a female pup is treated with testosterone during critical developmental behavior, she will show male-typical sexual behaviors; this treatment also prevents the expression of female-typical behaviors in adulthood

9. Chapter 10 • Example of organizational effects (luteinizing hormone response): • In female rats, an increase in estrogen levels during first part of estrous cycle is followed by the release of a hormone (luteinizing hormone, LH) from the pituitary gland; this does not occur in males (even if they are treated with a high dose of estrogen) • LH is required for the final maturation of the developing oocyte in the ovaries; without LH, follicle and oocyte it contains will die • A nucleus called the AVPV, which is located at the very front of the hypothalamus, plays a major role in the LH surge in response to estrogen; neurons in the AVPV have estrogen (and progesterone) receptors; damage to this area in females prevents the LH surge • Sexual dimorphism: in rats, AVPV is larger in females than in males; this nucleus is rich in androgen receptors; interestingly, testosterone appears to have a negative effect on the development of this nucleus, as evidenced by its smaller size in males • Critical period for the organization of the luteinizing hormone response to estrogen appears to extend from birth to the 10th day of life; this period occurs later than the critical period for the masculinization of the SDN of the MPOA in male rats; it should be noted that testosterone inhibits development of the AVPV, whereas it promotes the development of the SDN of the MPOA

10. Chapter 10 • Diversity in sexuality is found among males and females: some males are more sexually active than others, and some females are more receptive/proceptive than others • Anderson: males rats that are more active have, on average, larger sexually dimorphic nuclei than less active males • Maternal stress effect: • Ingebord Ward: Stress on mother rat leads to males that are less sexually active in adulthood than male offspring of females who were not stressed (maternal stress demasculinizes male rats) • Under normal conditions, testosterone levels peak at around the 18th & 19th day of development (at onset of critical period for masculinization of SDN-MPOA); In stressed females, the testosterone peak is disrupted—it occurs much earlier at around the 16th & 17th day of development • Thus, in male offspring of stressed mothers, testosterone levels during critical developmental period may not be sufficient to masculinize SDN-MPOA; in most cases, the SDN of these males is intermediate in size between the typical male and the typical female nucleus  the result is males that display less male-typical behaviors (and more female-typical behaviors) than other males

11. Chapter 10 • Other influences on sexual development: • Mother rats spend time licking anogenital region of pups; they lick the anogenital regions of male pups more than female pups; this stimulates testosterone production. Male pups that are exposed to abnormally low rate of licking will be less sexually active than males rats that ,as pups, are exposed to normal (or higher) rate of licking • Male juvenile rhesus monkeys must interact with other juveniles in order to develop into sexually competent individuals • Goy: if young rhesus monkeys are reared in isolation from their peers, they fail to show the “double foot-clasp mount,” and they fail to mount females when they are adults • Although these behaviors are dependent on organizational effects of androgens on the brain, they also require an environmental factor (social interaction) • Kallman’s syndrome: characterized by inability to smell & delayed onset of puberty; Delayed puberty is caused by absence or defective function of LHRH-producing neurons of the hypothalamus. LHRH neurons originate in olfactory mucosa and they migrate to hypothalamus; the major defect in these individuals occurs in the cells of the primitive olfactory epithelium (that’s why they can’t smell), and the cells that originate from there migrate to the hypothalamus are also defective (that’s why puberty is delayed)

12. Chapter 11 • Most nonsexual differences between males and females are statistical in nature (considerable overlap) • Aggression is a sex-differentiated trait: • Among mammals (including humans), males are generally more aggressive than females; females are aggressive under certain circumstances • Females: defense of offspring (maternal aggression) • Males: aggression can be goal-directed (e.g., to acquire food or mates), but much male aggression is just “for the hell of it” • Greater male aggressiveness is apparent in juvenile play—they engage in more rough-and-tumble play than females • These behaviors are dependent on prenatal androgen exposure (organizational effect), the expression of aggression in adult males is also dependent on increased levels of testosterone that occurs from puberty onward (activation effect); in fact, castration of males before puberty decreases these aggressive these behaviors

13. Chapter 11 • The amygdala is part of the limbic system and it is located in the anterior part of the temporal lobe, next to the hippocampus; it contains several nuclei • Corticomedial nucleus of the amygdala is involved in sexual behavior (lesions to this nucleus in male rats interferes with male sexual behavior • Basolateral nucleus of the amygdala plays a role in aggression (lesions of this nucleus reduce aggressive behaviors in both rats and primates; in addition, lesions of this region in juvenile monkeys reduce rough-and-tumble play) • Change from rough-and-tumble play to adult aggression may result from increased circulating androgen levels after puberty • Neurons in the amygdala contain androgen receptors • Maternal aggression • Although different from general adult male aggression, maternal aggression is also influenced by early androgen exposure; Early androgen exposure can have an organization influence on later maternal aggression • in female rats, those that, as developing fetuses, are exposed to testosterone from an adjacent male fetus, demonstrated increased maternal aggressiveness as adult mothers • In rodents, maternal aggression is increased during second half of pregnancy; this is due to high blood levels of progesterone during this time • Sensory input from the nipple promotes the expression of maternal aggression; suckling by pups after birth triggers maternal aggression

15. Chapter 11 • Visuospatial skills • Males tend to perform better than females at some tasks that require spatial or visuospatial skills • Male rats perform better in mazes than do females • Men outperform women, on average, on a variety of spatial tasks (e.g., mental rotation) • Verbal ability • Women tend to outperform men on some tests of verbal ability (differences are less dramatic than for spatial tasks) • Verbal fluency: women are generally better at rapidly producing a set of words that belong to a particular category • In both sexes, language is predominantly a function of the left hemisphere; however, women tend to use their right hemisphere more than men. The superior verbal abilities shown by women may reflect this difference between the sexes. This may also explain why women, in general, recover language better than men do after strokes affecting the left hemisphere

16. Chapter 11 • Are these differences between the sexes inborn or learned? • Some evidence that organizational effects of hormones may play a role • Women exposed to high levels of androgens while they were fetuses (e.g., congenital adrenal hyperplasia) score better than other women on spatial tests; they do not do worse on verbal tasks • Female rats that were given androgens around the time of birth perform better in mazes than untreated females • Androgen-insensitivity syndrome: Individuals with this condition are chromosomal males with functioning testes that secrete testosterone. However, they do not have functional androgen receptors—therefore the body develops in the female direction and these individuals are raised as girls • Individuals with this condition perform worse on visuospatial tasks than men; interestingly, they also perform worse than other women. These results suggest that even low levels of androgens present in normal females during development may function to improve spatial skills

17. Chapter 11 • Sexually dimorphic brain regions: • Corpus callosum (CC): is a major connection (made up of axons) between the left and right hemispheres; it is the same size in women and men. However, the CC occupies a larger fraction of the entire brain volume in women than in men, suggesting that the two cerebral hemispheres are more richly interconnected in women than in men • Anterior commissure (AC): Also an axonal connection between the hemispheres but smaller than the CC. It has been reported that the AC is larger in absolute size in women than in men, suggesting that the two hemispheres are more interconnected in women than in men • The stronger interconnection between both hemispheres in women may be related to women’s greater verbal fluency • LeVay: women are generally more “in touch with their feelings” than men; it may be that a larger corpus callosum and anterior commissure might make an individual better at expressing her or his feelings

20. Chapter 12 • Sexual orientation: the direction of sexual feelings or behavior toward individuals of the opposite sex (heterosexuality), the same sex (homosexuality), or some combination of the two (bisexuality) • People’s feelings don’t always coincide with their behavior • For example, prisoners who engage in homosexual activities because sexual partners of the opposite sex are not available (homosexual behavior/heterosexual feelings) • Another example would be married men or women who have homosexual feelings but cannot express these feelings because of religious convictions or a desire to conform (heterosexual behavior/homosexual feelings)

21. Chapter 12 • Alfred Kinsey • Sex researcher who in the 1940s & 1950s studied sexual behavior in American men & women (very controversial in its time) I • Men: 37% of male population had at least some overt homosexual experience to the point of orgasm; 10% were exclusively homosexual for at least 3 years of their lives; 4% were exclusively homosexual throughout their lives • Women: 13% of female population had at least some overt homosexual experience to the point of orgasm; 1-3% of unmarried women & 0.3% of married women were exclusively homosexual • Kinsey’s research was criticized for various reasons • Sampling issue—oversampled people who were or had been in prison; this may have led to an exaggeration of the numbers of bisexual individuals in the population • Leading questions—during interviews, his research team relied extensively on leading questions (e.g., instead of asking if the person had ever had a homosexual experience, the interviewer would ask “when was your first homosexual experience?”)

22. Chapter 12 • More recent studies: 4-5% of male population & 2-4% of female population are predominantly homosexual for a large part of their lives • Psychoanalytic perspective (early 20th century) • Freud: homosexuality is pathological state of arrested development due to defective parenting—inappropriate close-bond w/ mother and/or distant father • Isay: although some survey data indicate that gay men tend to recollect their fathers as hostile and distant & their mothers as unusually close, it may be that Freud confused cause and effect. That is, it is possible that a child’s gender atypical behavior may evoke negative reactions from fathers & positive ones from mothers

23. Chapter 12 • Homosexuality runs in families • 25% of all the brothers of gay men are themselves gay and 15% of the sisters of lesbian women are themselves lesbian, whereas in the general population the incidence of homosexuality is below 10% • Concordance for homosexuality is: 50-65% among male identical twins, 25-30% among male dizygotic twins, 48% among female identical twins, and 16% among female dizygotic twins • Klinefelter’s syndrome: male has extra X chromosomes (XXY); these males show much higher incidence of homosexuality than XY males. • Genetic factors can influence sexual orientation

24. Chapter 12 • Childhood traits are, to some extent, predictive of adult sexual orientation • Children who later become heterosexual tend to have sex-typical childhoods • Children who later become homosexual tend to have sex-atypical childhoods • Boys who are “sissy”, dislike rough games have a greater likelihood of becoming gay than other boys; boys with even stronger sexy-atypical traits (e.g., like to put on girl’s clothing) have an even greater likelihood of becoming gay • In women, the story is similar but less clear • The existence of childhood gender nonconformity as a predictor of adult homosexuality is very consistent with the idea that adult sexual orientation is influenced by the biological mechanism involved in sexual differentiation of the brain (under the influence of gonadal steroid hormones)

25. Chapter 12 • Biological basis of homosexuality? • Congenital adrenal hyperplasia: having this condition increases the likelihood that women will be lesbian or bisexual in adulthood; as mentioned previously, this condition also masculinizes play and mothering behavior • Men w/ XXY chromosome pattern (Klinefelter’s syndrome) have a much higher incidence of homosexuality than XY males; these men also report greater incidence of sex-atypical traits as children • High concordance for homosexuality among identical twins • Other (environmental/social) influences cannot be ruled out

26. Chapter 12 • Homosexual & heterosexual individuals differ in more than simply who they like to have sex with • Visuospatial skills: gay men’s performance at the mental rotation task is on average closer to that of women than that of heterosexual; it is less clear whether gay men have an equivalent superiority in tests of verbal skills—some studies have found that gay men tend to score like heterosexual women • Cerebral functions of gay men are more symmetrically distributed to the left and right hemispheres than they are in straight men. • McCormick: reported that both gay men and lesbian women are less consistently right-handed, tending to either use their left hands preferentially or, more commonly, to do some tasks with the right hand, some with the left; these findings suggest that their cerebral functions may be less lateralized than those of heterosexual men and women • These findings are a bit puzzling: one would expect a different results in lesbian women (more lateralization of cerebral function, as in heterosexual men). More research is needed.

27. Chapter 12 • Are there differences in the anatomical or chemical structure of the brain between homosexual and heterosexual individuals? • LeVay’s research: He obtained the brains of gay men (all of whom had died of AIDS) as well as the brains of heterosexual men who had also died of AIDS (these were intravenous drug abusers) and of presumably heterosexual men who had died of other causes; he also obtained the brains of presumably heterosexual women • LeVay processed and analyzed hypothalamic brain tissue from these brains (he was blind to which specimen came from which group of subjects)

28. Chapter 12 • LeVay’s results: • INAH3, (interstitial nucleus of anterior hypothalamus #3) was on average two- to threefold bigger in the presumed heterosexual men (irrespective of cause of death) than in women, confirming previous findings by other researchers • In gay men, INAH3 was on average the same size as in the women, and two to three times smaller than in the straight men • It is possible that the smaller size of this nucleus in gay men was caused (or influenced) by AIDS; this does not appear to be the case since LeVay also used a control group of heterosexual patients who had died of AIDS—these men had a larger INAH3 • In addition, none of the other hypothalamic nuclei (e.g., INAH 1,2, & 4) showed differences between groups; LeVay also mentioned that there were no dying cells, inflammatory reactions, or other signs of pathological processes; • Others factors should be considered: are gay men who die of AIDS representative of gay men as a whole, or are they atypical? after publication of his study, LeVay analyzed hypothalamic tissue from a gay man who died of a disease other than AIDS—this individual’s INAH 3 was smaller than normal • It is not possible, on the basis of LeVay’s observations, to say whether the structural differences were present at birth, and later influenced men to become gay or straight, or whether they arose in adult life, perhaps as a result of the men’s sexual behavior

29. Chapter 12 • It was previously mentioned that levels of circulating androgens act on neurons of the SDN-MPOA of male rats during a critical developmental period • It may be that there are differences between gay and straight fetuses in the levels of circulating androgens during the critical developmental period of INAH 3 • Alternatively, androgen levels may be the same, but neurons of the INAH 3 in gay men may respond differently to hormones • LeVay: thinks it’s responsiveness to the hormones, not hormone levels, that is important • Gunther Dörner: believed that sexual orientation depends on prenatal interaction between sex hormones and the brain • He claimed that gay men respond to estrogen injections with a female-typical surge in luteinizing hormone secretion, while straight men do not; however, this has only been replicated by 1 of 3 studies • In addition, this LH surge, which is characteristic of rats, may not exist in humans or other primates at all • He also proposed that maternal stress is a key factor in the etiology of male homosexuality

30. Chapter 12 • If there are genes that influence people to become homosexual, why do such genes exist and why have they been perpetuated? • In theory, “gay” genes should be selected against because they induce nonprocreative sexual behavior • Kin selection: although “gay” genes reduce direct reproductive success of the individual who possesses them, it can cause that individual to promote the reproductive success of his or her close relatives • “sickle-cell” model: heterozygotes have an advantage (i.e., having a single copy of the “gay” gene may be advantageous under certain circumstances) • variant genes re-created as the old ones are eliminated