what do gnrh neurons recieve input from in the perinatal period and what does this cause
developing neural GABA-glutamte innervations and glia
ARC Kiss neurons
causes mini puberty of early infancy
sexual dimorphism of Kiss1 neurons in AVPV
female has a lot more neurons than male
castration/ovareactomy effect on sexual dimorphism of these neurons
when both given exogenous oestrogne
still showed sexual dimorphism
so its not due to sex steroids, but occurs during development
diff between males and females in critical period of brain developement
aroudn tim eof birth
males have high testosterone levels
females have very low sex steroid levels
what is the organisational hypothesis
high testosterone levels in critical phase = masculinisation of the kiss1 expression = deletion of kiss1 AVPV neurons
low oestrogen = feminisation = lots of kiss1 in AVPV
how can we prove organisational hypothesis
if male mouse castrated at birth, low testosterone levels means feminisation of the brain - lots of kiss1 in avpv
how long is critical period in mice/rats
10 dias
what happens to gnrh expression during juvenile period
ARC Kiss neurons are supressed
lack of gnrh expression
mechanism of kickstart of puberty in rodents
- inc in no. kiss1 neurons in hyothal, inc projections to gnrh neurons
- inc endogenous kisspeptin release therefore full activation of gnrh/gonadotropin axis
- kisspeptin receptor (GPR54)’s signalling efficiency also enhanced
- inc in sensitivity to stim effects of kisspeptin on GnRH
what kickstarts the increase of kiss1 neurons
oestrogen
the kiss1 itself does not trigger puberty, only amplifies
what happens in peripubertal period to arc kiss neuron input
‘brake’ is lifted, stim ARC Kiss neuronal input reinstated
what enables the generation of the gnrh surge in pubertal period
late development of kiss neurons, project from preoptic area to gnrh cell bodies = generation of gnrh surge and surge in LH
what do people with obesity/type2 diabetes usually have
altered kisspeptin levels in hypothalamus
what can subnutrition/unctrolled diabetes lead to in terms of kiss1
lowered kisspeptin levels in hypothalamus
therefore reduction in HPG axis and reduction in reporoductive success
external kisspeptin can rescue the reproductive effects but NOT the metabolic
effects
if kiss1 doesnt fully control metabolism, then what does
leptin
what is leptin
- a hormone released from adipose tissue, - proporitonal to amount of fat in body
- signal of energy abundance
- stimulates GnRH activation
what are ob/ob mice
congential lack of leptin
no leptin receptors found on GnRH neurons
what did ob/ob mice show about kiss1 neurons
the ARC ones express leptin receptors
(the ob/ob mice have a suppression of kiss1 expression)
what happens when leptin treatment given to obob mice
partially rescues defective kiss1 levels in brain
reason for menopause in rodent
- defect in lh surge
- decrease in oestrogen
- less +ve feedback on Kiss1 in AVPV
reason for menopause in humans
- decrease in sex steroid production in ovaries
- increase kiss1 in arc
- increase in gonadotropin production
- inc FSH and LH
- doesnt translate to sex steroid production
what is menopause linked to in females
neurodegenerative diseases
increased gonadotropin levels in blood
how does inc testosterone correlate to amygdala
increased amygdala size
what is slow drop in testosteron in morning effect on adolecent male brains
inc anxiety, depression, attention problems
