Lecture 27: Puberty Flashcards by Hannah Kim

Describe the characterisitics of Puberty

Growth and maturation of p_rimary sexual characteristics_ (gonads and genitals).
Appearance and maturation of s_econdary sexual characteristics_
Adolescent growth spurt occurs
Fertility is achieved
Profound psychological effects are observed!

These changes result directly or indirectly from

Maturation of the hypothalamic-pit gonadotropin unit
Stimulation of the sex organs
Secretion of sex steroids

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Puberty changes result directly or indirectly from

Maturation of the hypothalamic-pit gonadotropin unit
Stimulation of the sex organs
Secretion of sex steroids

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What are the first signs of Puberty in Girls and Boys?

1) Breast development
2) Grwoth spurt
1) Increasd testicular enlargement
2) >3ml (orchidometer)
3) Growth spurt later

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When do the different puberties occur?

Axis wakes up 3 times.

1) Fetal life
2) First few months of life
3) In Adolescence

Puberty is expected to be suppressed - active (Gonadostatin?)

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If a girl is less than ____ years old, it is considered to be early

8 (although this is early)

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What is the word for “breast development”?

Thelarche

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What is the ord for “pubic hair development”

Pubarche

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What is the word for “Gonadal development”

Gonadarche

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What is the word for “First menstual period”

Menarche

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What is the word for “breast development in boys”

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Describe the STAGES of Gential Development in boys

Stage 1:

No development

Stage 2:

1) Scrotum becomes a bit bigger
2) Testes become bigger
3) Scrotal skin becomes thinner

Stage 3

1) Penis starts to enlarge

Stage 4

1) Scrotum becomes a bit darker

Stage 5

ADULT

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Describe the stages of Pubic Hair Development (Boys)

Stage 1: No pubic hair at all

Stage 2: Just become more coarse than normal hair

Stage 3: Longer and curlier

Stage 4: Lifted and widened

Stage 5: Lots of pubic hair

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Describe the Tanner Stages of breast development

(Mostly describing the areola not the size of the breast)

Stage 1: No development

Stage 2: Earliest- breast bud

Stage 4: Areola lifts up from the breast

Stage 5: Comes down again

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Puberty is driven by…

_________ more specifically, ___________ nucleus

HPA axis

Median preoptic nucleus in the hypothalamus

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Describe the HPA feedback loops in girls

1) The hypothalamus makes GnRH which travels down to the gonadtroph cell in the anterior pituitary
2) Gonadotroph cell produces FSH and LH
3) LH binds to receptors in the Theca cells which are in the stroma of the ovary. These theca cells make androgens in response (e.g. testosterone)
4) FSH triggers the granulosa cells to aromatase testosterone to estradiol
- also produce progesterone (negatively feedback on the hypothalamus and pit)
- also produce inhibin which feeds back and inhibits the production of FSH and LH (just pit)

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Describe the HPA feedback loops in boys

GnRH

LH and FSH

LH binds to leydig and produces testosterone (negative feedback on GnRH and pit)

FSH binds to sertoili cells and produces inhibin (negative feedback on pit)

Describe the LH and FSH release during early, mid and late puberty (separately)

Early

Topic phase increases
Night pulses begin

Mid-puberty

Greater increase in tonic phase
Higher amplitude night pulses

Late-Puberty

-Day and night pulses

If a child has early-puberty. What can you give them?

Activator of GnRH

Constant binding of GnRH shuts down the whole system

When is the Gonadaostat on for off?

Fetal Life

Gonadostat is off
Hypothalalmus makes lot of GnRH
Strong affect on goands
Weak negative feedback

Childhood

Everything is clamped down.
gonadostat is on

Some GnRH produced

Small effect on gonads
Large negative feedback

Puberty

-Everything unclamps

Describe the changes in hormones as a child transits into puberty

Gonadostat is turned off.
Increased pulsatile GNRH and LH/FSH secretion.
Increased s_ex steroid_ production.
Reduced sensitivity to n_egative feedbac_k from sex steroids.

By early puberty, hypothalamus is released from ___________control.

By early puberty, hypothalamus is released from gonadostat control. The mechanism of this release remains unclear. The hypothalamus and pituitary also become less sensitive to the inhibitory effects of sex steroids.

Note that median preoptic nucleus produces GnRH.

Describe the Gonadostat

I_ntrinsic CNS inhibitory mechanism._ S_ex steroid dependent (turn it off)._

γ aminobutyric acid (GABA) appears to be a potent inhibitor of pulsatile GNRH secretion.

In prepubertal monkeys, GABA receptor blocker leads to rise in GnRH.
Glutamate —(GAD)—> GABA
Enzyme GAD is detectable in median basal eminence

Describe Kisspeptin

Kisspeptin is product of KISS1 gene. It also has a role as metastasis suppressor gene.

Kisspeptin expressing neurons located in arcuate nucleus, periventricular nucleus, preoptic nucleus.
Kisspeptin neurons send projections into the preoptic nucleus (triggering GnRH cell bodies).

Kisspeptin is n_aturally occurring ligand_ for GPR54. G protein coupled receptor 54 (GPR54) regulates GnRH secretion and or release from hypothalamus.

Kisspeptin as puberty trigger, according to evidence to support this concept:

GPR54 mutations leads to failure to go into puberty.
Kisspeptin administration to prepubertal rats stimulates LH and ovulation.
KISS1 and GPR54 expression increased at the start of puberty.

Kisspeptin can also cure infertility due to hypothalamic problems due to its potent stimulation of GnRH.

Kisspeptin is product of KISS1 gene. It also has a role as metastasis suppressor gene.

Kisspeptin expressing neurons located in _____nucleus, _______nucleus, ______nucleus.
Kisspeptin neurons send projections into the ______nucleus (triggering GnRH cell bodies).

Kisspeptin is naturally occurring ligand for _____________ receptor 54 regulates ______secretion and or release from hypothalamus.

Kisspeptin is product of KISS1 gene. It also has a role as metastasis suppressor gene.

Kisspeptin expressing neurons located in arcuate nucleus, periventricular nucleus, preoptic nucleus.
Kisspeptin neurons send projections into the preoptic nucleus (triggering GnRH cell bodies).

Kisspeptin is naturally occurring ligand for GPR54. G protein coupled receptor 54 (GPR54) regulates GnRH secretion and or release from hypothalamus.

Kisspeptin as puberty trigger, according to evidence to support this concept:

GPR54 mutations leads to failure to go into puberty.
Kisspeptin administration to prepubertal rats stimulates LH and ovulation.
KISS1 and GPR54 expression increased at the start of puberty.

Kisspeptin can also cure infertility due to hypothalamic problems due to its potent stimulation of GnRH.

What kick starts puberty?

**_Kisspeptin as puberty trigger,_** according to evidence to support this concept: * GPR54 mutations leads to failure to go into puberty. Kisspeptin is product of KISS1 gene. It also has a role as metastasis suppressor gene. * Kisspeptin expressing neurons located in arcuate nucleus, periventricular nucleus, preoptic nucleus. * Kisspeptin neurons send projections into the preoptic nucleus (triggering GnRH cell bodies). Kisspeptin is naturally occurring ligand for GPR54. G protein coupled receptor 54 (GPR54) regulates GnRH secretion and or release from hypothalamus.

Describe Inhibin

Inhibin stimulated by FSH, and it is a _negative feedback to FSH secretion._ It is produced by _sertoli_ cells (m), _granulosa_ cells (f). *Dimer, 2 chains, α and β (variable). A and B forms with identical function.*

Describe Adrenarche

When adrenal glands 'wake up'- DHEAs _↑ adrenal androgen production (DHEAs)_ (*weak androgen*) occurs in _late childhood (_8-10 years). * Temporal association with puberty, _NOT a sign of puberty_. * _Produces pubarche (_pubic hair development). * Trigger unknown.

Is the development of pubic hair a sign of the beginning of puberty in girls?

No.- begins with breast development Adrenarche (increased production of DHEAS- produces pubarche)

What causes Pubarche?

**Adrenarche-\> ↑ adrenal androgen production (DHEAs)** (*weak androgen*) occurs in late childhood (8-10 years). * Temporal association with puberty, _NOT a sign of puberty_. * **_Produces pubarche (_**pubic hair development). * Trigger unknown.

Describe Leptin and its change in puberty

Leptin (leptos = thin) is an adipostatic hormone (produced by the adipocytes)_(↑leptin with ↑fat mass_). May be a facilitatory signal (about how much change) to _influence timing of puberty_. _Obese children_ have _earlier onset of puberty_. *In girls 1 kg wt gain lowers age of menarche by 13 days.* _Leptin levels peak_ just prior to _onset of puberty in boys._ Leptin deficient mice never achieve puberty, however leptin treatment induces puberty.

Compare the differences between a patient who is leptin resistant and someone who is leptin deficient

If we are leptin resistance, then _high leptin_ (body obese, brain starved) due to _disrupted feedback loop_, t**_hus obese._** If we are l_eptin deficiency,_ then _low leptin_, _triggers hunge_r and _keeps eating_ thus **_obese_**.

What is the pattern of age of menarche?

Age of menarche is getting younger, and directly correlated with body fatness. There is wide racial variation with body fatness, hence menarche age. *Menarche now are 11.5 yrs US black, 12.3 yrs USA white, 12.8 yrs UK. Fallen in USA by 0.34 yrs in past 25 yrs.*

Describe the differences in body composition between males and females before and after puberty

**Prepubertal** male is _equal_ to female in terms of lean, skeletal and fat mass. When **puberty**, _male_ tends to be lean mass, skeletal mass (1.5x\>F). _Female_ tends to be more fat mass (2x\>M) due to E2. * Fat: _males truncal,_ f_emales generalised._ * Hips: _enlarge in females._ Increased bone mineral density in puberty with peak bone mass achieved in early 20s. Female bone mass increases quicker than male due to E2.

What are the Pubertal growth factors?

(All increased) 1) Sex steroids 2) Growth hormone 3) IGF-1 4) Isulin