HPG axis 1 Flashcards
reproductive potential in males and females
males have a greater reproductive potential (until death)
where are GnRH neurons located
preoptic area and arcuate nucleus in hypothalamus
where is GnRH released
pituitary portal blood system
LH and FSH release
release from gonadotroph cells in anterior pituitary in response to GnRH at regular phases
LH in males and females
males - stimulates testosterone in testes
females - stimulates oestrogen, controls reproductive cycle and reproduction
FSH in males and females
males - growth/maturation of testes and spermatogenesis
females - growth/maturation of ovarian follices
GnRH in foetal development
occurs in olfactory placode E10.5
olfactory neurons in nasal placodes send axons back then GnRH neurons migrate
kallman syndrome
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
GnRH neuronal populations
only few thousand in brain
not tightly grouped - mostly scattered in hypothalamus
majority in defined regions
GnRH neuronal cell bodies
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
GnRH cell lines
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
GnRH cell coordination
regular electrical pulses coordinate with LH pulses in blood
pulse generator between cells
GnRH neurons connected to eachother (besides from median eminence)
highly interconnected despite scattered (long dendritic connections between cells)
why is GnRH released as pulses
prevents receptor sensitisation
allows LH and FSH to be controlled individually
what are the 2 variables in GnRH release
amplitude
frequency
administer GnRH injections
LH released at same frequency
reduced pulse frequency = increased LH pulse amplitude
lesion GnRH neurons in rats
LH only responds to regular pulses
continuous GnRH infusion has no effect on LH release
steroid feedback in males and females
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
oestrogen positive feedback
high levels needed for LH surge
LH surge cause ovulation
day 11-14
negative feedback of steroid hormones
administer hormones (oestrogen) to suppress GnRH pulses and LH pulses causing negative feedback
castration of gonads
increases GnRH frequency
sex steroid hormones do not affect GnRH synthesis
receptors on the GnRH neurons
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
administration of oestrogen
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
combined effect of oestrogen release
acts on GnRH and gonadotroph cells
increased LH surge triggers ovulation
after ovulation oestrogen reverts back to positive feedback
