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Sex/gender differences in humans

Sexual differentiation of the

brain

Sex differences in other primates Strange anatomical sex difference

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Are there sex differences in human

Human sex differences
brains?
• Amygdala (M>F)
• INAH3 (M>F)
• Preoptic area (M>F)
• Suprachiasmatic nucleus (different shape)
• Anterior commissure (F>M)
• Cerebellum (M>F)
• Cortex neuron number (M>F)
• Cortex synapses and dendrites (F>M)
• Hippocampus (F>M)
• Wernicke’s and Broca’s areas (F>M)

Sex difference in neurotransmitters Some species have more dramatic

and receptors sex differences

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Alfred Jost learns that testes secrete Sex

SRY gene
masculinizing factor determination
• The sex-determining region of
the Y chromosome (SRY) codes
for testis-determining factor
• TDF initiates the formation of
the testes
– In the absence of TDF, ovaries
form

Differentiation of internal genitalia Testosterone secretion in males

• If testes: testosterone and
anti-mullerian hormone
prenatally
– T causes Wolffian ducts to
develop into male internal
organs
– AMH causes Mullerian ducts to
degenerate
• Lack of T and AMH: female
internal organs

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T is often converted to E within

Steroid hormone biosynthesis
neurons
• Testosterone
can be
converted to
estradiol
with only
one enzyme
(aromatase)

Estrogen receptors in the brain Importance of perinatal

testosterone
• Surges of testosterone also masculinize and
defeminize the brain
• The ovaries are quiescent until puberty, so
female phenotype is the default

• The hypothalamus and limbic system are full of

estrogen and androgen receptors
• These areas are also the most sexually dimorphic

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Control of gonadal hormone Actions of steroid hormones in

secretion after puberty neurons
• GnRH release from the
• Can influence membrane
hypothalamus causes LH
excitability, sensitivity to
and FSH release from the
neurotransmitters or
anterior pituitary
neurotransmitter release
• LH and FSH cause estradiol – Very quick actions
and testosterone release
• Can bind to intracellular
from the ovaries and testes
steroid receptors to alter
• Negative feedback shuts transcription
down GnRH secretion – Longer-lasting
• HPG activity modulated by
light cues

Hormones can also affect cause

Hormones can affect neuron size
more subtle changes

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Sexual differentiation of the

Organizational actions of hormones
hypothalamus
• Occur during a critical period (usually
perinatally or during puberty)
• Long-lasting (often permanent) changes to
brain and behavior
• Effect may not be present until years later
• Generally not reversible
• Usually changes are in macro structure
(number of neurons, synapses, etc.) • The sexually dimorphic nucleus of the preoptic area
• We’ll look at 4 examples: SDN-POA, AVPV, (SDN-POA) is larger in males than in females
SNB, song control nuclei • Probably important for male sex behavior

Perinatal hormones affect SDN-POA Female-biased sexual dimorphism in the

anteroventral periventricular nucleus of the
volume hypothalamus (AVPV)
inactivated

• Probably important for ovulation and maternal behavior

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In some areas of the brain (POA), In other areas (AVPV), T induces

neonatal T prevents cell death apoptosis

• Also occurs through the

conversion of T to E
• Females have less
apoptosis, so larger volume

• In the POA, T is converted to E,

which then blocks apoptosis
pathways

Sex differences in the spinal The SNB develops

nucleus of the bulbocavernosus due to trophic
factors released
by muscles in the
presence of
testosterone

Onuf’s nucleus also sexually dimorphic in

humans

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SNB Sexual dimorphism in zebra finch

differentiation song control nuclei
requires
activation of
androgen
receptors

Posthatching Phytoestrogens and xenoestrogens

exposure to
estradiol results in
larger HVC in
females

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Activational effects of hormones Sex differences in the medial amygdala

• Temporary effects on the brain and behavior • Male MeA

– Effect disappears after hormone disappears
much larger
than female
• Usually not a critical period
MeA
• Usually changes micro structure (activates
• Due to
2nd messenger cascade or effects synapses)
changes in
• We’ll talk about the MeA, limbic dopamine circulating
neurons, sexual behavior/desire, LTP, and hormones in
arcuate peptides adulthood

Other limbic dimorphisms Some sex differences require

organizational and activational
effects of hormones

• Number of dopaminergic cells much higher in male

prairie voles
• Controlled by activational effects of hormones

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Changing sexual behavior by manipulating Manipulations only in adulthood were

perinatal and adult hormones not effective

+ T in
+ E and P in
adulthood
adulthood

POA and MeA important for male Hormonal cycles influence sexual
sexual behavior behavior in rats

• Female rats can ONLY have sex right after estradiol

peaks
• Coordinates sex with ovulation

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Sexual desire also highest around

Estradiol s affects on lordosis
ovulation in human females

• E acts in the hypothalamus to turn off the

inhibition of the lordosis reflex in the spinal cord

Activational effects of estradiol Activational effects of estrogens

also affect the hippocampus on food intake
• Food intake is lowest
when sexually receptive
– Right after peak in
estradiol

• Proestrus (high E levels) is associated with more

dendritic spines and an increased propensity for LTP

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Estradiol and arcuate peptide Sex differences in the human

expression hypothalamus may relate to sexuality

• The third insterstitial nucleus of the

anterior hypothalamus may be
• Estradiol at least partially decreases food analogous to the SDN-POA
intake by decreasing NPY and AgRP expression • Larger in straight men than in
women or gay men

Gender differences What happens when

in the limbic system differentiation occurs differently?
• Genetic aberration (XO, XXY, etc.)
• Mutation in enzymes for steroid hormone
biosynthesis or hormone receptors
• Translocation of the SRY gene

• The bed nucleus of the stria terminalis

(similar function to the amygdala) is larger in
men
• May relate to gender identity

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Androgen insensitivity syndrome

Congenital Adrenal Hyperplasia
(AIS)

• Mutation in the androgen receptor, such that it can t function

normally
• XY individuals, have testes, secrete testosterone, but no effects of
testosterone
– No internal genitalia, female-typical external genitalia
• Typically identify as women
• Fewer CAIS women identify as gay/bi than in non-CAIS population
• Mutation in one of the enzymes necessary for
glucocorticoid production leads to excess androgens
• Females typically have masculinized appearance
• Prevalence of gay/bi identity correlates with
exposure to prenatal androgens

Gynandromorph provided
evidence that genetic sex is Four core genotypes
important, too

• Some song control nuclei

were lateralized

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Some sex differences more

affected by gonadal hormones,
others by sex chromosomes
Pain response

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