Sex differentiation in the brain Flashcards
What happens in androgen insensitivity syndrome (AIS)?
- Androgen receptors do not work.
- Gonads develop as testes.
- Testosterone cannot perform its normal functions.
What are the characteristics of individuals with 46, XY and androgen insensitivity syndrome?
- Anatomically female but lack internal female genitalia.
- Typically identify as women.
- Puberty may be delayed, treated with hormone supplements.
What happens in 5α-reductase deficiency?
- 5α-reductase converts testosterone into DHT.
- DHT is essential for prenatal external genital development.
What are the effects of 5α-reductase deficiency on individuals with 46, XY?
- Born with female external genitalia but male internal genitalia.
- At puberty, high testosterone levels mimic DHT, leading to male external genitalia development.
- After puberty, they mostly identify as men.
What is congenital adrenal hyperplasia (CAH)?
A condition causing high prenatal testosterone levels in 46, XX individuals, leading to:
- Ambiguous external genitalia.
- Treatment with steroids after diagnosis.
How does CAH affect gender identity in 46, XX individuals?
5% of CAH girls assigned female at birth experience gender dysphoria.
12% of CAH “girls” assigned male at birth also experience gender dysphoria.
What is the hypothalamo-pituitary-adrenal (HPA) axis’s role in CAH?
- CRH and ACTH stimulate excess androgen production by the adrenal glands.
- Treated CAH reduces excess androgen with hydrocortisone.
What factors contribute to structural and functional sex differences in the brain?
- Hormones (activational and organizational)
- Genetics (genes on sex chromosomes)
- Environment (e.g., peers, culture)
What was discovered about sex differences in mice?
- Genetic manipulation can separate genetic effects from hormonal effects.
- Cultural impacts are minimal; hormones and genetics are the biggest contributors.
What human conditions provide insight into sex differences in the brain?
Congenital adrenal hyperplasia (CAH) in 46, XX.
Complete androgen insensitivity syndrome (CAIS) in 46, XY.
Hormone treatment in transgender individuals.
How do toy preferences differ between boys and girls, and what role does testosterone play?
Boys tend to prefer cars; girls prefer dolls.
CAH 46, XX individuals have more masculine toy preferences.
CAIS 46, XY individuals have feminine toy preferences, suggesting a link to prenatal testosterone levels.
How do sex differences manifest in spatial mental rotation tasks?
Men typically perform better.
CAH 46, XX individuals perform better than non-CAH 46, XX individuals.
CAIS 46, XY individuals perform like non-CAIS 46, XX individuals.
What structural differences exist between male and female brains?
Male brains are approximately 10% larger.
Female cortex is thicker (more grey matter).
Males have larger white matter volume and subcortical structures.
CAIS 46, XY individuals display both masculine and feminine traits.
What are the main findings on sexual orientation and brain structure?
SCN (biological clock) is larger in androphilic individuals.
INAH-3 is smaller in androphilic individuals.
Anterior commissure is larger in androphilic individuals.
What are some environmental effects on sex differences in the brain?
Influences on brain development
Effects of practice (you improve at what you spend time doing)
Social effects
Little to no evidence that these affect sexual orientation
How do most people describe their experience of sexual orientation?
Most feel their sexual orientation has always been this way.
There is no good evidence to support effects of parenting or learning on sexual orientation.
What is the significance of male sheep in sexual orientation studies?
8% of male sheep are exclusively interested in other males.
The Sexually Dimorphic Nucleus (SDN) of the preoptic area is smaller in these males.
The size of the SDN is influenced by developmental testosterone levels.
Variations to study when looking at activational hormonal effects
Testosterone levels
Oestradiol levels
Menstrual cycle variations
What do activational hormonal effects influence?
No effect on sexual orientation
Can affect behaviors such as libido and sexual motivation through hormone fluctuations, manipulations, or treatments
When are testosterone (T) levels high in boys during development?
Weeks 8-24 of pregnancy:
Early: external genitalia development
Late: brain differentiation
First 3 months after birth:
Potential further brain development
Evidence for organisational role of hormones
Correlations with measured prenatal hormones
Correlations with adult traits linked to prenatal hormones
Conditions with varying prenatal hormone levels (e.g., CAH, androgen insensitivity syndrome)
Examples of embryonic T correlates:
Cognitive performance:
Androphile men: better verbal abilities, worse visuo-spatial performance
Gynophile women: faster mental rotation
2D/4D finger length ratios:
Male: 0.95, Female: 0.97
Butch lesbians: more masculine ratios
Androphile men: inconsistent findings, may correlate with gender non-conformity
Oto-acoustic emissions (OAEs):
Gynophile women’s OAEs closer to gynophile men’s than androphile women’s
What does CAH suggest about sexual orientation?
CAH females are more likely to identify as gynophile, suggesting early testosterone exposure influences sexual orientation
Findings from twin studies on sexual orientation
Higher concordance in monozygotic than dizygotic twins
Estimates range from 30-100%
Possibly higher concordance for women than men
Evidence from genetic mapping
Androphilic men often have androphilic maternal uncles
X-chromosome regions related to sexual orientation identified
Other chromosomes also implicated
Evolutionary concerns and mechanisms for maintaining genes related to sexual orientation
Homosexual individuals might have fewer offspring, yet the genes persist:
Heterozygote advantage
Different effects in males vs. females
Kin selection (genes passed through relatives)
Evidence: males with more older brothers from the same mother more likely to be gay, potentially due to maternal immune response to neuroligin 4 Y-linked protein
What are the conclusions about sexual orientation?
Clear biological developmental influences
No single influence is absolute
Many factors influence sexual orientation
How does gender identity differ from sexual orientation?
Larger sex difference
Not binary
Only 40% of childhood gender dysphoria persists after puberty
Influences on gender identity
No single phenotype
Genetic predispositions
Specific alleles linked to gender dysphoria
Pre-transition brain differences:
MtF: more feminine cortical thickness and white matter in some areas
FtM: more masculine basal ganglia and white matter tracts
Some differences distinct from cis males and cis females
Conclusions about sexual differentiation
Genetic and hormonal factors influence sexual differentiation
Brain and behaviour traits can be masculinised or feminised, resulting in diverse gendered trait combinations
