Lecture 13 (Luckman) Flashcards
model of puberty in rodents?
as puberty approaches, number of GnRH neurons increase.
increase in number of GPR54 receptors.
Increase in the number of kisspeptin neurons in the hypothalamus and their projections to GnRH neurons.
Elevation of the endogenous kisspeptine tone leading to full activation of the GnRH/gonadotropin axis.
Enhancement of GPR54 signalling efficiency.
Increase in the sensitivity to the stimulatory effects of kisspeptin on GnRH/LH responses.
what triggers puberty?
not kisspeptin.
early in juvenile state, something activates the ovares stimulating the production of oestrogen.
neurobiological brake model of puberty in primates
GnRH pulse generating mechanism resides in arcuate nucleus, has output to GnRH terminals in median eminence ME
Infant:
arcuate GnRH pulse is robust, leading to release of kisspeptin in ME, resulting in corresponding pattern of GnRH release into the portal circulation.
drives LH/FSH secretion to gonads.
Juvenile:
central inhibition/neurobiological brake holds arcuate GnRH pulse down.
Pulsitile release of kisspeptin in ME is suppressed.
therefore decreased GnRH release leads to decreased LH/FSH.
Puberty: Triggered when brake is removed. GnRH reactivated ME release of kisspeptin increases.
LH/FSH increase leads to gametogenesis.
Brake crucial for puberty.
Kisspeptin and metabolism
reproduction is highly demanding on energy reserves.
energy reserves/metabolic state crucial for modulating timing of puberty,
hypothalamic kisspeptin system is sensitive to changes in bodies energy status, suppresed by an imbalance such as malnutrition or uncontroller diabeetus.
fatfat makes infertile
leptin
fat hormone.
peptide hormone
synthesised and secreted by adipose tissue. secreted in body fat stores.
signals energy abundance.
stimulates activation of GnRH.
falls in concentration following weight loss.
Leptin deficient mice?
Ob/Ob mice:
Have a congenital lack of leptin
No leptin receptors found in GnRH neurons
Kiss1 neurons in the ARC express leptin receptor
Have suppression of Kiss1 expression in the ARC
Leptin treatment partially rescues defective Kiss1 levels in the brain
Leptin’s action on GnRH neurons in the hypothalamus may occur via Kiss1 neurons
Leptin’s role in puberty
adipose secretes leptin, activates kisspeptin neurons in ARC which activate GnRH neurons.
therefore leptin regulates puberty onset via regulation of kisspeptin expression in the hypothalamus
when obese lots of leptin means puberty onsets earlier.
kisspeptin and pregnancy
highest levels of peripherla circulating kisspeptin found in the placenta.
increases with gestation.
decrease in level of gonadotopin hormones but dont know why
placental receptors lower in women with recurrent miscarriage.
lmasma kisspep lower in 1st trimester in those who had miscarriage.
could be marker for miscarriage risk.
kisspeptin and lactation
inhibits kisspeptin expression/function.
suppression of mRNA in ARc during lactation. decrease in kisspeptin expression and decrease in responsiveness to kisspeptin by GnRH neurons. leads to inhibition of HPG axis.
Breastfeeding decreases pregnart chance.
kisspeptin and stress
inhibits reproductive function by suppressing GnRH release, unclear how, maybe hypothalamic corticotropin releasing hormone CRH.
↓ kisspeptin levels hypothalamus
↓ Gonadotropin secretion
↓ LH responses to kisspeptin
sexual differences in AVPV Kiss1 neurons
higher in female rats adult.
not due to sex steroids, gonadectomised male/females given the same oestrogen levels still show dimorphic expression in AVPV.
happens during critical period where testosterone release stimulates brain to develop in a masculine way
what is the organisational hypothesis?
↑Testosterone or oestrogen → masculinisation Kiss1 expression
↓ Oestrogen necessary for
Feminisation of Kiss1 neurons in AVPV
castration of newborn males removes increase in post natal testosterone, results in feminised neural populations.
likewise treatment to females with tesosterone results in masculinsed brain circuitry.
kiss1 AVPV sexual dimorphism
kiss1 levels in AVPV sexually dimorphic, feamles have big increase in puberty,
stimulatory effects of oestrogen on kiss1 AVPV neurons.
AVPV role in generating preovulatory surge of gonadotropins in females.
all suggest sexual dimorphism in kiss1 cells is AVPV is key for sexual maturation and brain sex differentation.
HPG axis senescence
in rodents, defective LH surge leads to less oestrogen + pos feedback on kiss1 neurons in AVPV.
decrease sensitivity of kisspeptin.
in humans, see a decrease in sex steroids, increase in kiss1 in ARC, increased gonadotropin release.
ageing linked to neurodegen diseases.
hormone replacement therapy delay alz?
Role of gonadal hormones on the adolescent brain
in adolescents increase in gonadal hormones leads to sexual maturation, leads to perminant changes to neural circuits. an imbalance in subcortical areas.
8-15 boys testosterone increases and correlated to increase in amygdala volume.
circadian rhythm in plasma testosterone increases at night.
