HPG axis 1

Question 1

reproductive potential in males and females

Answer 1

males have a greater reproductive potential (until death)

Question 2

where are GnRH neurons located

Answer 2

preoptic area and arcuate nucleus in hypothalamus

Question 3

where is GnRH released

Answer 3

pituitary portal blood system

Question 4

LH and FSH release

Answer 4

release from gonadotroph cells in anterior pituitary in response to GnRH at regular phases

Question 5

LH in males and females

Answer 5

males - stimulates testosterone in testes
females - stimulates oestrogen, controls reproductive cycle and reproduction

Question 6

FSH in males and females

Answer 6

males - growth/maturation of testes and spermatogenesis
females - growth/maturation of ovarian follices

Question 7

GnRH in foetal development

Answer 7

occurs in olfactory placode E10.5
olfactory neurons in nasal placodes send axons back then GnRH neurons migrate

Question 8

kallman syndrome

Answer 8

defect in olfactory system development
failure of olfactory axons to project to the forebrain so GnRH neurons fail to migrate to the hypothalamus
lack of puberty and adult reproduction and anosmia (no sense of smell)
affects 1:10,000 individuals

Question 9

GnRH neuronal populations

Answer 9

only few thousand in brain
not tightly grouped - mostly scattered in hypothalamus
majority in defined regions

Question 10

GnRH neuronal cell bodies

Answer 10

small (10-20nm)
sends many dendrites from cell body and axonal projections from POA/ARC to median eminence (base of hypothalamus)
forms terminals to release GnRH into pituitary portal bloodstream
GnRH released in regular pulses

Question 11

GnRH cell lines

Answer 11

GT1-7 cells (neuronal cell line) GnRH released in regular pulses
tag cells with GFP - measure electrical activity of individual GnRH neurons
regular spontaneous action potential in pulses
inherent phasic rhythms

Question 12

GnRH cell coordination

Answer 12

regular electrical pulses coordinate with LH pulses in blood

Question 13

pulse generator between cells

Answer 13

GnRH neurons connected to eachother (besides from median eminence)
highly interconnected despite scattered (long dendritic connections between cells)

Question 14

why is GnRH released as pulses

Answer 14

prevents receptor sensitisation
allows LH and FSH to be controlled individually

Question 15

what are the 2 variables in GnRH release

Answer 15

amplitude
frequency

Question 16

administer GnRH injections

Answer 16

LH released at same frequency
reduced pulse frequency = increased LH pulse amplitude

Question 17

lesion GnRH neurons in rats

Answer 17

LH only responds to regular pulses
continuous GnRH infusion has no effect on LH release

Question 18

steroid feedback in males and females

Answer 18

males - consistent levels of circulating gonadal steroids (primarily testosterone) long term negative feedback
females - circulating levels of gonadal steroids change across reprodcutive cycles (mainly oestrogen) mostly negative feedback, positive feedback possible

Question 19

oestrogen positive feedback

Answer 19

high levels needed for LH surge
LH surge cause ovulation
day 11-14

Question 20

negative feedback of steroid hormones

Answer 20

administer hormones (oestrogen) to suppress GnRH pulses and LH pulses causing negative feedback

Question 21

castration of gonads

Answer 21

increases GnRH frequency
sex steroid hormones do not affect GnRH synthesis

Question 22

receptors on the GnRH neurons

Answer 22

no androgen receptor
no oestrogen R-a
some GnRH express oestrogen R-B (not all)

LH and FSH synthesis is directly inhibited by steroid hormones

Question 23

administration of oestrogen

Answer 23

initially - inhibits LH and FSH release
more administration - stimulatory effects (FSH and LH release), inhibits GnRH pulse and frequency, baseline gets higher
LH secretory granules move to cell surface not FSH secretory granules

Question 24

combined effect of oestrogen release

Answer 24

acts on GnRH and gonadotroph cells
increased LH surge triggers ovulation
after ovulation oestrogen reverts back to positive feedback