Puberty

Question 1

What do gonadotropins do in the neonatal period? How?

Answer 1

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.

Question 2

During most of childhood, FSH and LH are low. Why?

Answer 2

GnRH is not being released.

it’s not being suppressed by negative feedback from gonads

Question 3

How do we know that the gonads aren’t suppressing GnRH levels in childhood?

Answer 3

Agonadal children have normal FSH and LH levels.

Question 4

What is used as a marker for GnRH?

Answer 4

LH, because of its short half-life.

GnRH can’t be measured easily

Question 5

What’s the major endocrine change of pre-puberty?

Answer 5

Return of GnRH pulsatility.

Question 6

What is the pattern of GnRH pulsatility in pre-puberty? How does this compare that in adults?

Answer 6

Pulses occur only at night.
(eventually lower amplitude pulses start showing up during the day)
In adults, the pulsatility is constant throughout the day.

Question 7

What drives menarche?

Answer 7

Sufficient estrogen to induce endometrial proliferation.

Question 8

What’s a common difference in cycles for the first 2 years after menarche vs. later?

Answer 8

Cycles are often anovulatory. (but not often enough to keep lots of girls from getting pregnant)

Question 9

What’s adrenarche? What is it responsible for?

Answer 9

Increase in androgen (DHEA) secretion from zona reticularis of adrenal gland.
Leads to growth of axillary and pubic hair.

Question 10

What’s gonadarche? What is it responsible for?

Answer 10

Activation of sex steroid release from gonads.

Leads to breasts and sexual maturation.

Question 11

Do you need functioning gonads for adrenarche? Classic example?

Answer 11

Nope. Women with Turner Syndrome still hit adrenarche.

Question 12

Do you need adrenal glands for gonadarche? Does early adrenarche mean early gonadarche?

Answer 12

Nope and nope.

Question 13

What is thelarche?

Answer 13

Breast development.

Question 14

What is pubarche?

Answer 14

Development of axillary and pubic hair.

Question 15

Of the “-arches,” which occurs first?

Answer 15

Adrenarche

Question 16

What is the order of “-arches” in most women? What’s a common variation?

Answer 16

Adrenarche
Thelarche (breasts)
Pubarche
Menarche
(somtimes pubarche will happen before thelarche)

Question 17

What drives breast maturation?

Answer 17

Estrogen, with maybe a little bit of progesterone at the end involved with pigmentation.

Question 18

Racial differences in puberty?

Answer 18

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.

Question 19

99ish percent of girls show first sign of sexual development within which years?

Answer 19

8 - 13

if outside this, merits further evaluation

Question 20

Why can girls get pregnant before menarche?

Answer 20

Ovulation can occur without menstruation.

Question 21

Take home point about the relationship between menstruation and ovulation early in puberty?

Answer 21

Either can happen without the other.

Question 22

How long after thelarche do you worry about not having menarche?
And thus by what age not having menarche would you always be worried?

Answer 22

2 years

Worry if no menses by 16 (or maybe 15).

Question 23

Average age of menarche in US? Is it still changing?

Answer 23

12.8 years

It’s actually been stable there for the past 40 years.

Question 24

5 categories of factors influencing onset of puberty?

Answer 24

Genetic
Environmental
Toxic
Nutritional
Hormonal

Question 25

3 reasons we think there’s a genetic component to age of menarche?

Answer 25

Correlation between age at menarche among mother-daughter and sisters.
Higher MZ concordance than DZ.
Racial differences.

Question 26

3 environmental factors associated with earlier puberty? (2 are weird)

Answer 26

Urban environment (may reflect more nutrition and less exercise)
Lower altitudes
Proximity to equator

Question 27

How does nutrition status affect age at menarche?

Answer 27

More excercise, less nutrition -> delayed menarche.
Obesity -> earlier menarche.
Severe obesity -> delayed menarche.

Question 28

How is obesity thought to affect menarche?

Answer 28

Estrogen is made in adipose tissue. High estrogen makes for early menarche. Very high estrogen can suppress gonadotropins.

Question 29

Toxins affecting onset of puberty?

Answer 29

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…

Question 30

What model is currently favored for the cause of the return of GnRH pulsatility at puberty? One reason why?

Answer 30

Removal of inhibition of GnRH release.

GnRH mRNA and peptide levels are similar before and after puberty.

Question 31

4 factors that may be involved in this putative inhibition of GnRH release?

Answer 31

GABA
Neuropeptide Y
Leptin
Kisspeptin

Question 32

What’s GABA do to GnRH? (3 pieces of evidence)

Answer 32

GABA appears to inhibit GnRH release.
GABA declines as GnRH increases at gonadarche.
GABA agonists can reverse precocious gonadarche.

Question 33

Evidence for Neuropeptide Y (NPY) being what inhibits GnRH?

Answer 33

When you add NPY to monkey brains, GnRH pulses are inhibited.
Gene expression are inverse to GnRH levels.

Question 34

Even if NPY doesn’t drive normal gonadarche, when does it (probably) suppress gonadarche?

Answer 34

Might suppress gonadarche in undernutrition. Leptin (marker of being fed) suppresses NPY.

Question 35

Why do we think leptin might drive gonadarche? Vague consensus as to its role?

Answer 35

Increases during childhood until puberty. Receptors go away after puberty.
Consensus?: Leptin is necessary for gonadarche, but doesn’t drive GnRH release.

Question 36

What is Kisspeptin’s receptor?

Answer 36

GPR54 (Kiss1)

Question 37

Evidence for Kisspeptin initiating gonadarche?

Answer 37

LoF mutations in GPR54 (receptor) -> no puberty.
Activating mutation in GPR54 -> precocious puberty
Kisspeptin seems to show up near GnRH neurons around puberty.