Lecture 2 (Louden)

Question 1

GnRH function in rodents?

Answer 1

GnRH is synthesised in hypothalamic neurones and released as pulses into the portal system. It causes the release of LH and FSH

Sex steroids and gonadal peptides (inhibin) feedback to regulate pituitary activity.

GnRH also acts directly on the brain and facilitates lordosis behaviour in females when directly injected.

Thus, the peptide controls both pituitary gonadotrophins and also sexual behaviour

Question 2

what can produce an LH surge?

Answer 2

only female rodents - due to sexual differentiation of the brain.

Question 3

what experiments were carried out to determine only female rodents can produce an LH surge?

Answer 3

1933:

Pfeiffer – ovarian transplants to the eye capsule of rat

OBSERVED: Ovulation only in females

1950-60: Harris – male pituitary transplantation to female pituitary, dimorphism persisted

CONCLUDED: Dimorphism resides in hypothalamus and regulates activity of pituitary.

1959: Phoenix and co-workers – Ovariectomised hamsters

Lordosis restored by oestrogen and progesterone only in females.

CONCLUDED: Sexual dimorphism of behavioural response

Question 4

what is lordosis?

Answer 4

Arches back

Elevates head

Reflexive behaviour to
allow male to mate

occurs on the day of ovulation.

Question 5

how does lordosis occur?

Answer 5

low oestrogen
growth of follicle (from FSH)
high oestrogen
progesterone
mating

oestrogen followed by progesterone

Question 6

what happens to lordosis if the ovaries are removed?

Answer 6

won’t occur.

however if an ovariectomy and repeated oestrogen for 2 days, then 1 injection of progesterone can make female exhibit lordosis 6h later.

Question 7

can males show lordosis?

Answer 7

no therefore brains are differentiated between the two sexes.

shown through castrating male and given oestrogen/progesterone, no lordosis.

Question 8

what is the organisational hypothesis?

Answer 8

Pheonix 1959
early androgens permanently alter the developing brain.

therefore sex steroids therefore organise the secondary sexual characteristics (ie penis/genitalia) and organise the brain.

The brain remains sensitive long after secondary sexual characters are formed.

Question 9

support for the organisational hypothesis?

Answer 9

treat female guinea pigs with prenatal testosterone, repeat with normal hormonal regime, do not show lordosis.

Question 10

what is the window of sensitivity to androgrens for rats?

Answer 10

10 days post natal.

Question 11

how can the female brain be masculinsed pre natally?

Answer 11

testosterone.

also oestrogen, no effect on genitalia, but more potent and effective at masculinising females brains.

challenges organisational hypothesis

Question 12

what produces sex steroids in male rodents?

Answer 12

leydig cells (in fetal testis)

Question 13

how is testosterone converted into oestrogen?

Answer 13

via aromatase, adds hydroxyl on outer ring.
makes aromatic

single step, hard to reverse it.

Question 14

what does the conversion of testosterone to oestrogen lead to?

Answer 14

sexual differentiation of the brain.

Question 15

what does the conversion of testosterone to 5DHT lead to?

Answer 15

development of external genitalia.

Question 16

what part of the brain is rich in cells expressing aromatase activity?

evidence?

Answer 16

hypothalamus

Radiolabelled testosterone can be recovered from the hypothalamus as radiolabelled oestrogen.

Question 17

what is the aromatisation hypothesis?

Answer 17

Aromatised oestrogen metabolites of testosterone masculinise the brain.

(then no LH surge)

Question 18

how is masculinisation of the female brain prevented during pregnancy?

Answer 18

High concentrations of maternal oestrogen are produced during pregnancy

Sex steroids readily pass through the placental barrier

Alpha fetal protein (AFP) binds maternal oestrogen and prevents passage through the placenta

Question 19

how does AFP work?

Answer 19

binds oestrogen, does not cross cytoplasm into nucleus of target neuron.

endogenous oestrogen can have a weak activation of receptor driving gene expression and feminisation of the brain.

review on Puts et al 2006 “Defending the brain from oestrogen. Nature Neuroscience 9, p155

Question 20

what effect does AFP have on males?

Answer 20

none as doesn’t recognise testosterone.

Question 21

why do female rodents injected with oestrogen masculinise in relation to AFP?

Answer 21

AFP get’s overpowered, can’t control such a high dose.

Question 22

AFP in primates?

Answer 22

doesn’t bind oestrogen, different structure.

therefore aromatisation may not play a strong role in masculinisation of human brain.

Question 23

how do masculinzed females and non masculinized males act?

Answer 23

neonatally castrated (CX) males behave like females, allow mounting.

whereas females treated early in life with testosterone (T) or its aromatized metabolite estradiol (E2) behave like males, mount.

Question 24

anatomical differences between male/female brains in rats?

Answer 24

medial preoptic nucleus
male much larger.

because the testes secrete testosterone during the perinatal sensitive period. After that time, testosterone has little effect on SDN-POA volume.

In contrast, the volume of the rat posterodorsal medial
amygdala (MePD), which is about 1.5 times larger in
males (c) than in females (d), retains its responsiveness
to testosterone throughout life.

Question 25

difference in corpus collosum in humans between sexes?

Answer 25

more bulbous splenium, later lectures.

Question 26

finger length human differences?

Answer 26

Women tend to have
similar length index finger
(2D) relative to ring
fingers (4D) or longer index.

Men tend to have longer
ring fingers (4D) compared
to index fingers.

This is a consequence of
prenatal exposure to
testosterone.

Question 27

apoptosis in male brains of rats?

Answer 27

Steroid reduces naturally occurring cell

death, resulting in more neurons surviving in males than in females.

Question 28

what is the SNB?

Answer 28

spinal nucleus of the
bulbocavernosus.

Before birth, the SNB system
is present in both male and
female rats, and motor neurons have established a
functional neuromuscular junction.

early exposure to testosterone maintained, broken in females

erection

These motor neurons in the lumbar spinal cord innervate striated muscles that attach to the base of the penis.

Male rats have more and larger SNB motor neurons than do females.

Question 29

how is the SNB kept alive in males/not in females?

Answer 29

die unless treated with testosterone.

One hypothesis is that testosterone induces the muscles to produce a trophic factor that preserves the muscles and either the same factor or an additional factor preserves the motor neurons.

Although adult SNB motor neurons possess androgen receptors, the primary effect of testosterone is to prevent death of the target muscles, which then secondarily spare SNB motor neurons from apoptosis.

Thus, testosterone does not act directly on SNB neurons to keep them alive.

Question 30

what are the bulbocavernosus muscles?

Answer 30

both sexes, contributes to erection of penis and clitoris, contractions of orgasm.