Brain differentiation Flashcards
Phoenix 1959
Classic animal studies & organisational hypothesis.
Ovariectomy = no lordosis. But then 2 days of OE infusion & single injection of P = lordosis.
Males = no effect.
So sex steroids prime female brain for sex-specific behaviour - occurs as male & female brains organised differently by action of sex steroids during development.
Prenatal AD in females = no lordosis in response to injections. Brain has been masculinised during window of sensitivity during development.
Booth 1977
Single injection of OE masculinises brain (10-100x more potent!)
Led to aromatisation hypothesis.
Aromatisation hypothesis
Testes produce T in males which crosses BBB & is locally converted to OE by aromatase (substitute -OH for =O)
Aromatase = high activity in ht.
Radiolabelled T can be recovered from ht as OE, some of which bound to OERs.
OE floods the brain & triggers male-like gene expression which masculinises some structures and defeminises others.
So therefore it is aromatised OE derivated from T that masculinises the mammalian brain.
Puts (2006)
AFP = neuroprotective protein. Binds OE & stops passage through BBB so foetal female brain protected from OE.
Develops feminised structures instead (probably occurs postnatally due to OE from ovaries, AFP no longer needed).
Balzhazart 2011
Prenatal exposure to T = male & female rats more masculinised e.g. increased mounting behaviours and less likely to show feminised behaviours.
Also sexual orientation in humans could be linked to prenatal AD exposure e.g. homosexual women = higher exposure.
Breedlove 2004
Male rats = larger SDN-POA due to testes secreting T in sensitive period only.
OE binds to OERs in brain & modulates gene expression to prevent apoptosis in SDN-POA.
Much larger SBN (in females muscles atrophy so motor neurons die).
T acts on androgen receptors to trigger production of protective trophic factors so SBN preserved in males.
1.5x larger MePD in amygdala, retains sensitivity to T through life & modulates male sexual arousal.
Castrate = MePD shrinks within 30 days.
Female treated with male T levels = MePD grows to male size within 30 days.
AVP neurons innervate rat LS (pair bonding & parental behaviour): increased innervation in males.
AVPN larger in females so T facilitates apoptosis.
Increased OT innervation of BST & NAc (pair bonding, maternal & social behaviour).
Breedlove 2010
Human males also have larger SDN-POA.
Human females have larger splenium.
Finger length sexually dimorphic - direct consequence of prenatal AD exposure.
Lower 2D:4D ratio = more male-like behaviours, aggression, homosexual in women, ADHD etc.
Bakker 2006
AFP-/- = masculine brain.
Treatment with drug that blocks OE synthesis = rescued female phenotype.
Shows AFP fully excludes OE from foetal female brain.
Gorski 1983
Single dose of OE to newborn female rat = no ovulation, no lordosis in response to hormone treatment.
Window of sensitivity.
Holloway 2001
Neurosteroids (OEs) that masculinise bird brains are synthesised locally in brain, occurs even with in vitro brain slices. Both necessary and sufficient to masculinise avian brain.
Not reliant on gonadal sex steroids (birds who have had gonadectomy still have same sexually dimorphic structures).
Arnold 2004
Gynadromorphic zebra finches - testes on right & ovary on left. HVc still more masculine on right side despite common steroidal signal so must be due to genetic differences.
Sex chromosomes = direct action on sex differentiation of brain cells.
So rely on chromosomal mechaniams rather than hormonal, like mammals.
Mazur 1998
Prenatal T levels associated with aggression in men.
Genomic imprinting
SRY gene on Y chromosome imprints male phenotype upon foetus. Secretes T so develops as male (female = default).
Bao & Swaab 2011
Differentiation of sexual organs occurs much earlier in gestation than sexual differentiation of the brain, so in rare cases can have different outcomes.
Brain structures represent that of gender identity, not sexual organs.
= Neurobiological theory of transsexuality.
Sexually dimorphic brain structures in zebra finches
RA (archistriatum nucleus) is larger in males. Axons from HVc don’t innervate RA properly unless exposed to OE which allows neuron proliferation & synapse formation.
So males = song nuclei much more developed.
Treat females with OE = can sing.
