PSY337: Neurobiology of Sexual Behaviour Lecture outline Popular belief & base rate of homosexuality Genetic Studies of homosexuality Sexual differentiation Sexual Anomalies Variables that effect gender

Two theories of gender identity Aromatization Location of SDN in rats Effect of testosterone on SDN Location of INAH nuclei in humans LH response & sexual orientation Bem's developmental theory of sexual orientation Evolutionary theories of homosexuality References & online materials Supplementary material Feedback

Lecture outline

• Before you begin you might like to review the lecture on Psychosexual Differentiation
• Popular beliefs about development of homosexuality.
• Base rate of homosexuality in population.
• Genetic Studies:Homosexuality in twins (Bailey et al, 1991).
• Aversion therapy as a treatment for homosexuality in the 1960s.
• Differentiation of the external genital organs (see  Carlson).
• Anomalies
  • Androgen insensitivity syndrome (See  Carlson)
  • Adrenogenital syndrome (see Carlson)
• Sexuality
  • gender role: adoption of behavioral traits that are deemed appropriate or characteristic of a particular sex
  • gender identity: personal perception of sex
  • Sexual orientation: attachment of erotic desire for member of same or different sex
  • Variables that effect gender
• Two theories of gender identity (Hines, Psychological Bulletin, 92, 56-80, 1982)
• Organisational effects of hormones (See Carlson) & Psychosexual differentiation: Year 1 Lecture Support Material
• Feminised male rats & masculinised female rats
• Aromatisation (See Carlson, )
• Organisation & Activational Effects of Hormones - A Simplistic View:
  • Organisational effects are permanent
  • Organisational effects occur in neonatal critical periods
  • Organisational effects are asymmetric to the sexes
  • Activational effects are linked to hormone presence
  • Activational effects are symmetric
  • For a more complete picture see Arnold, Hormones & Behavior, 19, 469-498, 1985
• Location of the sexually dimorphic nucleus of the preoptic area
• Effect of hormones on the sexually dimorphic nucleus (SDN) of the preoptic area (Figure 10.16 from Carlson)
• Hypothalamic cell groups in homosexual men (Le Vay, Science, 1991, 253, 1034-1037)
• Gladue et al, Science, 1984, 225, 1496-1499 studied release of LH in response to estrogen in homo- and heterosexual men, results suggest that homosexual men show evidence of partial demasculinisation
• The debate moves on: In the 23 October, 1997 issue of Nature, Dr Marc Breedlove of the University of California, Berkeley provided an insight into the following important issue.
  Does the influence of genes and hormones mould the brain in such a way to affect sexual orientation? Or might sexual activity itself alter the brain?
  "Breedlove studied male rats that copulated freely with constantly receptive females, and compared the structures of certain nerve tracts in their spinal cords with those of male rats caged with unreceptive females, and which therefore did not have the opportunity for intercourse. The nerve tracts studied by Dr Breedlove are known to be influenced by sexual factors, notably the presence of the male sex hormone testosterone. The result was clear -- sexual activity has an effect on the structure of the nervous system. The relevant nerve tracts were smaller in males that were free to copulate than in those that remained celibate. "
  You can read more about this important piece of research in the Nature article Lifelines: Sex on the brain by Henry Gee

Popular belief & base rate of homosexuality

.. 43% of Americans believe that 'young homesexuals became that way because of older homosexuals'

 
In an interview with Science in 1992 Bailey stated:
'No one has ever found a postnatal social environmental influence for homosexual orientation - and they have looked plenty'

Changes in the psychiatric status of homosexuality

• Until the early 1970's the study of homosexuality remained mostly in the domains of psychiatry. Different theories about the origins of homosexuality were advanced. Most of the theories associated homosexuality with psychopathology, caused by faulty upbringing, which included a domineering mother, a detached father or both. Inaccurate as this assumption was, it was not surprising because psychiatrists obtained their data only from people in therapy who had mental or emotional problems.
• In 1972 & 73 the American Psychiatric Assoc. deleted homosexuality as a disease from their diagnostic handbooks.
• The term "sexual preference" was introduced in the 1970's to correct the earlier concept that homosexuality was a disease or deviation.
• After 1982, as more scientists found evidence that homosexuality & heterosexuality may not be a matter of free choice, the term "sexual orientation" emerged & is commonly used today.

Genetic Studies of homosexuality

• One of the most frequently cited studies of homosexuality was that of Kallmann in 1952[Kallmann F. "Comparative Twin Study on the Genetic Aspects of Male Homosexuality", J Nerv Ment Dis. 1952. 115:283-298. ]. He reported a one hundred percent concordance in identical twins for homosexuality, and only twelve percent concordance in fraternal twins (identical twins result from a fertilised egg splitting in half and each half continues to grow as an embryo. Thus, the identical twins have an identical genetic code. Fraternal twins do not have identical genetic codes as each twin arises from different fertilised eggs). Subsequent studies have failed to repeat Kallman's findings. Kallman later himself postulated that this impressive concordance was an artefact due to the fact his sample was largely drawn from mentally ill, institutionalised patients[Kallmann F. In Discussion: Ranier J, Masnikoff A, Kolb L, Carr A. "Homosexuality and Heterosexuality in Identical Twins" Psychosom Med. 1960. 22:251-259 ] .
• The largest twin study was published by Bailey and Pillard[ Bailey J, Pillard R. "A Genetic Study of Male Sexual Orientation", Arch Gen Psychiatry , 1991. 48:1089-1096. ] and received considerable media coverage.
  This study included
  • 56 pairs of identical twins,
  • 54 pairs of fraternal twins,
  • 142 non-twin brothers of twins and
  • 57 pairs of adoptive brothers.

  They found that the concordance rate of homosexuality for

  • genetically unrelated adoptive brothers was 11%
  • for non-twin biologic brothers about 9%
  • the rate for fraternal twins was 22%
  • and for identical twins it was 52%

Point to ponder: If homosexuality is due to a person's genetic make-up, how could the gene survive? Surely it would have disappeared due to homosexuals fathering less children?

Sexual differentiation

We covered this material previously. It is reproduced here for your convenience.
In early interuterine development males and female external genitalia (visible sex organs) are identical. Under the influence of the androgen dihydrotestosterone the external genitalia develop in the male direction. In the absence of androgens female external genitalia develop. The crucial point about these diagrams is that tissues that are equivalent for the two sexes in the undifferentiated state will become different organs by the time of birth. You can follow this change by tracing the fates of the different coloured tissue.

• The top diagram shows the undifferentiated state.
• The middle diagrams shows diffferentiation beginning during the seventh and eighth weeks of pregnancy.
• The bottom diagrams show complete differentiation of the external genitalia at birth.

An important message from this diagram is that - regardless of genetic sex -

• a child will develop female external genitalia unless it is exposed to dihydrotestosterone
• a child will develop male external genitalia if it is exposed to dihydrotestosterone

	In early intrauterine development male and female external genitalia (visible sex organs) are identical.
	Under the influence of the androgen dihydrotestosterone, the external genitalia develop in the male direction. In the absence of androgens female external genitalia develop.
	The crucial point about this diagram is that tissues that are equivalent for the two sexes in the undifferentiated state will become different organs by the time of birth. You can follow this change by tracing the fates of the different coloured tissue. The top diagram shows the undifferentiated state. The middle diagrams shows differentiation beginning during the third and fourth months of pregnancy. The bottom diagrams show complete differentiation of the external genitalia at birth. These diagrams are based on the drawings found in most textbooks that cover the the biological bases of sexual behaviour.

Here is an animated diagram of the effects of androgen exposure on external genital development that will open in a new browser window.

Sexual Anomalies:

Frequency

• Males:
  • 5-alpha-reductase deficiency
    • produces ambiguous genitals: labia (with testes inside) & enlarged clitoris
    • common in an area of Dominican Republic
    • raised as girls, at puberty, hidden testes secrete T causing penis & scrotum to grow (urethra at base of penis)
    • little difficulty making transition to male gender roles
  • Testicular feminization syndrome (TFS) or androgen insensitivity syndrome (AIS)
    • individual has external female genitalia caused by mutation on X chromosome
    • insensitivite to androgens
    • testes develop in response to TDF (contained within abdomen)
    • Mullerian tract regresses in response to MRH but Wolffian system does not develop
    • diagnosis often occurs at puberty when there is a failure to menstruate
    • individual is sterile
    • treatment is usually to remove the testes and give estrogens to induce secondary female sex characteristics
  • Klinefelter Syndrome
    • has XXY chromosomes
    • sexed as male
    • usually sterile because of reduced sperm production
    • underdeveloped genitalia and may be some breast development
  • XYY
    • incidence 1 in 850 male births
    • some mental retardation and unusual height
    • may be sterile
    • a high proportion found in prison populations, this might be because of increased aggressiveness caused by extra Y chromosome
    • incidence of aggressiveness in XYY males in general population not found to be higher than average so large prison population probably results from other factors such as lower intelligence
• Females:
  • Turner Syndrome:
    • has XO chromosomes
    • incidence 1 in 3000 female births
    • congenital lack of (or destruction of) 2nd X chromosome
    • sexed as girls
    • abnormal ovaries must be treated with estrogens to induce puberty
    • slow growth, hearing loss, mental retardation, kidney dysfucntion, neck webbing
  • Congenital adrenal hyperplasia (CAH) or adrenogenital syndrome (AGS)
    • lack of 21-hydroxylase enzyme which converts cholesterol to cortisol
    • excess cholesterol converted to androgens
    • may also be caused by exogenous steroid administration during pregnancy

    
    Diagram showing the endocrinological cause of CAH

    
    
    Patients suffering from CAH
    
    

Variables that effect gender:

The eight Variables of gender:

1. Chromosomal gender
2. Gonadal gender
3. Prenatal hormone gender
4. Internal accessory organs
5. External genital appearence
6. Pubertal hormone gender
7. Assigned gender
8. Gender identity

Two theories of gender identity

Each of us has a gender identity - a private feeling that we are male or female. There are two fundamentally different explanations for how this develops.

The most influential theory is that our gender is the result of environmental influences, particularly the way we are treated by our parents, guardians, friends and relatives. According to Dr John Money we are psychosexually neutral at birth, and our gender is a consequence of the nurture we receive as children.

The less popular view is that gender may is the result of nature, particularly the effects of hormones on the developing brain.

This is not a dry academic argument. The lives of a significant number of people have been changed as a result of the application of these theories.

Aromatization

Steroid hormones such as testosterone and estrogen pass through the cell membrane and bind with intracellular steroid receptors. This complex then passes into the nucleus where it activates mRNA transcription which leads to the production of proteins.The proteins then leave the nucleus and pass into the cell cytoplasm.

In some cells of the body the effects of testosterone are carried out by estrogen. Testosterone is aromatized to estrogen, which activates estrogen receptors in the nucleus. In females alphafetoprotein captures estrogen so that it cannot cross the cell membrane and androgenise the female brain.

The following account of the aromatization hypotheis is adapted from Milgram.

"The aromatization hypothesis is an attempt to explain how brain masculinization is caused by high levels of estrogen, which affect estrogen receptors in brain cells.  According to the aromatization hypothesis, masculinization of some brain structures results from the conversion of testosterone to estrogen by an aromatase enzyme (aromatization). This hypothesis was originally proposed to account for the findings that:

• high levels of estrogen act like testosterone in leading to defeminization; and
• dihydroxytestosterone does not mimic the effect of testosterone.

Testosterone and dihydroxytestosterone differ in their response to aromatase enzyme; only testosterone is converted to the aromatic compound estrogen.  Thus, dihydroxytestosterone does not produce defeminization.

If this hypothesis is correct, why aren't the brain of young females, who secrete estrogen, masculinized?  One reason may be that ovarian secretion of estrogens are lower than testicular secretion of testosterone. Another factor that serves to prevent the aromatization of estrogen is a protein known as alpha-fetoprotein, which binds to estrogens but not testosterone and restricts the access of estrogens to estrogen receptors in the brain. This suggestion is supported by evidence of high levels of alpha-fetoprotein in young female rodents."

Location of SDN in rats

• The sexually dimorphic nucleus of the preoptic area of the hypothalamus is much larger in male rats than in females.
• Use the animation to discover the position of this sex difference in the rat brain.
• Click on static images to reveal names of important areas in the brain

Use arrow / slider to rotate brain	Sagittal view of rat brain	Coronal section of rat brain

Common abbreviations:

• SDN : sexually dimorphic nucleus
• POA : preoptic area
• SDN-POA : sexually dimorphic nucleus of the preoptic area

Effect of testosterone on SDN

Photomicrographs of sections through the preoptic area of the rat brain. SDN-POA = sexually dimorphic nucleus of the preoptic area

Neonatal hormone exposure influences volume of sexually dimorphic nucleus. Females androgenised with testosterone proprionate (TP) on day 4 have dose-related significantly larger volume than control (oil-treated ) females; volume is reduced in neonatally castrated males as compared with males castrated on day 21. Redrawn from Gorski, In Kreiger & Hughes (Eds), Neuroendocrinology

Anatomic dimorphism in preoptic area of hypothalamus of intact and castrated male rats and female rats treated with testosterone or oil. Data from Raisman & Field.

Location of INAH nuclei in humans

There are four interstitial nuclei of the anterior hypothalamus (INAH) in the human brain that may be homologues (similar in structure and evolutionary origin) of the rat's sexually dimorphic nuclei (SDN).

This diagram shows a coronal section through the human hypothalamus at the level of the optic chiasm (OC). The four cell groups (INAH1, 2, 3 and 4) studied by Le Vay, (Science, Vol 253, page 1034, 30th August 1991) are indicated by the corresponding numbers.

Le Vay (1991) reported that: INAH3 is larger in heterosexual men than in  women assumed to be heterosexual INAH3 is larger in heterosexual men than in homosexual men INAH3 is similar in size in homosexual men and heterosexual women However it is quite difficult to interpret these results: many of the homosexual men died of AIDS - what is the effect of AIDS on INAH3 size? does a small INAH3 cause homosexuality? or does homosexuality reduce the size of INAH3? Is some unknown 'third factor' responsible for homosexuality and reduced INAH3 volume? These results have not been replicated by an independent group of scientists

Caveat! This table (redrawn from Byne, 1994) shows that there is no clear agreement between researchers in which INAH nuclei differ between the sexes.

Researchers	Brain region
	INAH1	INAH2	INAH3	INAH4
Swaab & Fliers, 1985	Larger in men	Not studied	Not studied	Not studied
Allen et al, 1989	No sex difference	Larger in men than in some women	Larger in men	No sex difference
LeVay, 1991	No sex difference	No sex difference	Larger in heterosexual men than in women or homosexual men	No sex difference

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LH response & sexual orientation

A neuroendocrine component, the positive estrogen feedback effect, thought to be related to sexual orientation and, indirectly, to sexual differentiation, was evaluated in healthy, noninstitutionalized research volunteers.  Men and women with a lifelong heterosexual orientation and men with a lifelong homosexual orientation were administered an estrogen preparation known to enhance the concentration of luteinizing hormone in women but not in men.  The secretory pattern of luteinizing hormone in the homosexuals in response to estrogen was intermediate between that of the heterosexual men and that of the women.  The diagram shows changes in LH in response to a single injection of Premarin. From: Gladue et al, Science, 225, 1496-1499, 1984. The interpretation of these results have been challenged and more recent studies have failed  to replicate the effect (Bem, 1996).

Bem's developmental theory of sexual orientation

In a recent article Bem (1996) has argued that nature sets the scene for nurture to determine sexual preferences:

Abstract: "A developmental theory of erotic/romantic attraction is presented that provides the same basic account for opposite-sex and same-sex desire in both men and women. It proposes that biological variables, such as genes, prenatal hormones, and brain neuroanatomy, do not code for sexual orientation per se but for childhood temperaments that influence a child's preferences for sex-typical or sex-atypical activities and peers. These preferences lead children to feel different from opposite- or same-sex peers--to perceive them as dissimilar, unfamiliar, and exotic. This, in turn, produces heightened nonspecific autonomic arousal that subsequently gets eroticized to that same class of dissimilar peers: Exotic becomes erotic. Specific mechanisms for effecting this transformation are proposed. The theory claims to accommodate both the empirical evidence of the biological essentialists and the cultural relativism of the social constructionists."

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Evolutionary theories of homosexuality

"...natural selection should favor heterosexuality as it facilitates reproduction and the propagation of genes. .... what has maintained homosexuality in a small but consistent percentage of the human population?" (Muscarella et al. 2001)

Muscarella et al. (2001) review several evolutionary theories of homosexuality:

• "The first and most widely recognized evolutionary theory of homosexuality is that of E. O. Wilson and is based on the concept of kin selection (i.e., a sociobiological explanation for the evolution of altruistic behaviors). This theory holds that during the course of human evolution homosexual individuals may have helped family members, through direct or indirect provision of resources, to reproduce more successfully than they would have otherwise. Thus, genes for homosexual behavior would have been propagated indirectly through relatives." (p 394)
• "Ross and Wells propose that homosexual behavior is an ‘exaptation’ of homosocial behavior. An exaptation is not a direct product of natural selection but a neutral variation of a behavior, which with time demonstrates some fitness enhancing quality. As a result, natural selection acts upon it. According to Ross and Wells, male homosocial behavior could have contributed to male survival through increased social support and access to resources. Homosexual behavior would have reinforced homosocial bonds and thus would have been acted upon by natural selection. would interact with a range of personal experiences, ecological conditions, and psychological processes resulting in a general sexual orientation." (p 395)
• "Kirkpatrick argues that homosexual behavior comes from individual selection for reciprocal altruism, which would have contributed to resource exchange and a reduction in inter-male aggression." (p 395)
• "Rahman and Wilson propose that variations in genotypes produced hominid males who were more feminine in behavioral traits and bisexual in sexual preferences. These characteristics contributed to same sex affiliation and females were attracted to these traits because they were associated with decreased aggression and infanticide, and increased parenting behavior. Over time, females chose increasingly feminine traits in males, which led to the evolution of alleles associated with exclusive homosexual interest. The contribution of the feminine traits to parenting and the viability offspring offset the reproductively deleterious effects in males." (p 397)

It strikes me that Rahman and Wilson's  theory predicts that

• women should prefer to mate with bisexual men, and
• most men should be bisexual

Supplementary material

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