Puberty Flashcards
What do gonadotropins do in the neonatal period? How?
Gonadotropins are high after birth for up to 2 years, leading to transient E and T secretion.
Gonadotropins are high because they’re released from suppression by maternal E and P that happened in utero.
During most of childhood, FSH and LH are low. Why?
GnRH is not being released.
it’s not being suppressed by negative feedback from gonads
How do we know that the gonads aren’t suppressing GnRH levels in childhood?
Agonadal children have normal FSH and LH levels.
What is used as a marker for GnRH?
LH, because of its short half-life.
GnRH can’t be measured easily
What’s the major endocrine change of pre-puberty?
Return of GnRH pulsatility.
What is the pattern of GnRH pulsatility in pre-puberty? How does this compare that in adults?
Pulses occur only at night.
(eventually lower amplitude pulses start showing up during the day)
In adults, the pulsatility is constant throughout the day.
What drives menarche?
Sufficient estrogen to induce endometrial proliferation.
What’s a common difference in cycles for the first 2 years after menarche vs. later?
Cycles are often anovulatory. (but not often enough to keep lots of girls from getting pregnant)
What’s adrenarche? What is it responsible for?
Increase in androgen (DHEA) secretion from zona reticularis of adrenal gland.
Leads to growth of axillary and pubic hair.
What’s gonadarche? What is it responsible for?
Activation of sex steroid release from gonads.
Leads to breasts and sexual maturation.
Do you need functioning gonads for adrenarche? Classic example?
Nope. Women with Turner Syndrome still hit adrenarche.
Do you need adrenal glands for gonadarche? Does early adrenarche mean early gonadarche?
Nope and nope.
What is thelarche?
Breast development.
What is pubarche?
Development of axillary and pubic hair.
Of the “-arches,” which occurs first?
Adrenarche
What is the order of “-arches” in most women? What’s a common variation?
Adrenarche Thelarche (breasts) Pubarche Menarche (somtimes pubarche will happen before thelarche)
What drives breast maturation?
Estrogen, with maybe a little bit of progesterone at the end involved with pigmentation.
Racial differences in puberty?
Sequence seems to be the same, but timing may vary. E.g. African Americans on average have early breast development.
Confounding with SES isn’t known with confidence.
99ish percent of girls show first sign of sexual development within which years?
8 - 13
if outside this, merits further evaluation
Why can girls get pregnant before menarche?
Ovulation can occur without menstruation.
Take home point about the relationship between menstruation and ovulation early in puberty?
Either can happen without the other.
How long after thelarche do you worry about not having menarche?
And thus by what age not having menarche would you always be worried?
2 years
Worry if no menses by 16 (or maybe 15).
Average age of menarche in US? Is it still changing?
12.8 years
It’s actually been stable there for the past 40 years.
5 categories of factors influencing onset of puberty?
Genetic Environmental Toxic Nutritional Hormonal
3 reasons we think there’s a genetic component to age of menarche?
Correlation between age at menarche among mother-daughter and sisters.
Higher MZ concordance than DZ.
Racial differences.
3 environmental factors associated with earlier puberty? (2 are weird)
Urban environment (may reflect more nutrition and less exercise)
Lower altitudes
Proximity to equator
How does nutrition status affect age at menarche?
More excercise, less nutrition -> delayed menarche.
Obesity -> earlier menarche.
Severe obesity -> delayed menarche.
How is obesity thought to affect menarche?
Estrogen is made in adipose tissue. High estrogen makes for early menarche. Very high estrogen can suppress gonadotropins.
Toxins affecting onset of puberty?
Hormones in meats?
Pthalates in plastics -recall parents trying to ban plastic bottles. (Are there good schools that also don’t have insane PTAs?)
Others…
What model is currently favored for the cause of the return of GnRH pulsatility at puberty? One reason why?
Removal of inhibition of GnRH release.
GnRH mRNA and peptide levels are similar before and after puberty.
4 factors that may be involved in this putative inhibition of GnRH release?
GABA
Neuropeptide Y
Leptin
Kisspeptin
What’s GABA do to GnRH? (3 pieces of evidence)
GABA appears to inhibit GnRH release.
GABA declines as GnRH increases at gonadarche.
GABA agonists can reverse precocious gonadarche.
Evidence for Neuropeptide Y (NPY) being what inhibits GnRH?
When you add NPY to monkey brains, GnRH pulses are inhibited.
Gene expression are inverse to GnRH levels.
Even if NPY doesn’t drive normal gonadarche, when does it (probably) suppress gonadarche?
Might suppress gonadarche in undernutrition. Leptin (marker of being fed) suppresses NPY.
Why do we think leptin might drive gonadarche? Vague consensus as to its role?
Increases during childhood until puberty. Receptors go away after puberty.
Consensus?: Leptin is necessary for gonadarche, but doesn’t drive GnRH release.
What is Kisspeptin’s receptor?
GPR54 (Kiss1)
Evidence for Kisspeptin initiating gonadarche?
LoF mutations in GPR54 (receptor) -> no puberty.
Activating mutation in GPR54 -> precocious puberty
Kisspeptin seems to show up near GnRH neurons around puberty.
