Puberty

Question 1

What’s the Styne and Grumbach quote of puberty?

KNOW THIS SLIDE

Answer 1

1. Secondary Sex characteristics appear and mature
2. Adolscent Growth Spurt occurs
3. Fertility is achieved
4. Profound psychological effects are observed!

These changes result directly or indirectly from; and look at these to find the core issues resulting in puberty issues!

• Maturation of the HP gonatotrophin unit
• Stimulation of the sex organs
• Secretion of sex steroids

Question 2

What’s the definition of normal puberty?

Answer 2

• Central Activation of the H-P gonadal axis
• Progressive sequential changes
• Appropriate rate (over 3-4yrs)

All these things occur “in tempo”!!

Question 3

Whats the first signs of puberty for boys and girls?

Answer 3

Girls (1^st sign) :

1. Breast development because eostrogen is the trigger ~10.5 yr
2. Then Growth spurt
3. Period 2-3 years later ~13-14yr

Boys (1^st sign) :

1. Increased testicular enlargment ~11-12yr
2. >4ml (orchidometer)
3. Growth spurt later testosterone > eostrogen 2-3 yrs later ~13-14yr

Question 4

How many puberties do you have?

Answer 4

3 Puberties of life!!!!

All related back to LH, FSH and sexsteriods

1. Pre-natal: We have a huge amount of sex steroids, LH and FSH, (how else would little boys be born with a fallace?)
2. Infancy: another little puberty. Biys penile length increases, girls may have a little pubic hair or best budding
   
   • ​​Different to withdrawal bleeding/ baby period which is due to removal from mums high estrogen environment
   • Everything goes to sleep
3. Adolescent: big, well-known puberty.

Question 5

What inhibits puberty throughout childhood?

Answer 5

The Gonadostat.

• An area of the brain that actively inhibits puberty
  
  • ​not able to find if you cut the brain up
• Tonically inhibits throughout childhoduntil at some point it starts to loss that inhibition → 3^rd puberty takes off.
• Any damage to this area →early puberty
  
  • if you’re in a car accident and hit your head, or kids wiht meningitis

Question 6

What do these terms mean?

Thelarche

Pubarche

Gonadarche

Menarche

Gynaecomastia

Answer 6

Thelarche: Breast development (breast budding in a girl)

Pubarche: Pubic hair development

Gonadarche: Gonadal development > makes a bit of eostrogen

Menarche: first menstrual period

Gynaecomastia: breast development in boys

Question 7

What is stage 1 of puberty in boys/girls?

Answer 7

Nothing, puberty has not yet begun

Question 8

What does this show us?

Answer 8

Boys reach a penile length of ~4-6cm relatively early on in life, and then stay there until adolescant puberty.

Why it’s hard to find obese boys penis’s

From 12-13yrs this begins to grow again.

Question 9

What happens if you damage/ injure the developing breast bud?

Answer 9

You can destry the entire breast development

Question 10

Normal Testicular Volume in boys?

Answer 10

There’s a wide range

Really big or really small → indicates pathological syndrome

Question 11

Leydig cells make?

Whats the best test of seminiferous tubule function is?

Answer 11

Testosterone and inhibin
**inhibin can be measure to see leydig cell function

Best test of SF tubule function: sperm count

If you’ve had chemo, you’ll be infertile before you become unvirilised

Question 12

What’s the impact off insulin on ovarian androgen production?

Answer 12

PCOS: Insulin resistant state

High levels of insulin intefere with their androgen production from thecal cells. Why they have male virilised symptoms.

Question 13

Why is it boys treated with chemo are infertile before they become unvirilised?

Answer 13

Leydig cells: only a very small proportion of testicular cells (1/5), so likely to be unharmed more then larger sertoli cells.

Question 14

Describe the LH and FSH release during puberty?

Answer 14

Early Puberty LH could be measured at 0 during the day

• Tonic phase increases
• Night Pulses begin

Mid Puberty

• Greater increase in tonic phase
• High amplitude night pulses

Late puberty Measure LH anytime and get a reading

• Day and night pulses

If on COCP, LH level will be 0, as cycle is switched off!

Question 15

A women who is having extremely irregular periods (~1yr) and we measured her LH levels and found them at 60 (extremely high)

What does this mean?

Answer 15

Tells us the ovaries have shut down = ovarian failure
Eg; women with Turners Syndrome

Nothing to do with brain as it is trying to compensate by increasing LH levels

Question 16

Describe the Childhood to puberty transition

Answer 16

• Gonadostat turned OFF (loss of inhibitory signal)
• Increased pulsatile GnRH → pulsatile LH/FSH
• Increased Sex steroid production
• Reduced sensitivity to negative feedback from sex steroids (in hypothalamus and pituitary)

Question 17

Describe Kisspeptin!

Answer 17

• Product of the KISS1 gene
  
  • ​Expressed where we think Gonadostat is
• Naturally occuring ligand for GPR54 receptor
• Also has a role as a metastasis suppressor gene
• Kisspeptin expressing neurons are located in:
  
  • Arcuate nucleus
  • Periventricular nucleus
  • Preoptic nucleus
• Therefore they project into GnRH producing areas
• KP neurons send prjections into the preoptic nucleus (GnRH cell bodies)

Question 18

What evidence supports Kisspeptin as a puberty trigger?

Answer 18

• GPR54 inactivating mutations → don’t go into puberty
  
  • have to give them GnRH
• If you give someone Kisspeptin → prepubertal get LH stimulation and ovulation
• KISS1 and GPR54 expression is increased at the start of puberty

Question 19

What stimulates inhibin and then what does it inhibit?

What is inhibin produced by?

Answer 19

Inhibin is stimulated by FSH, the acts as a negative feedback to the FSH secretion from Ant. pituitary.

Produced By:

• Sertoli cells(m)
• Granulosa cells (f)

Dimer, 2 chains a and B (variable)

A and B form with indenticle function

Question 20

What is Adrenarche?

Answer 20

• An increase in adrenal (weak) androgen production (DHEAS hormone)
  
  • Occurs in late childhood (8-10yrs) → pongy smell
• Temporal association with puberty, NOT AN ACTUAL SIGN/stage OF PUBERTY
• Produces pubarche (pubic hair development)
• Trigger is unknown

Big cause of anxiety for kids

Question 21

DHEAS is produced from?

What can we measure from the adrenal steroid?

Answer 21

DHEA gets sulphated → DHEAS

Dehydroepiandrosterone, is an endogenous steroid hormone. It is the most abundant circulating steroid hormone in humans, in whom it is produced in the adrenal glands

We can measure Aldosterone, cortisol, DHT, estradiol, DHEA, DHEAS

Question 22

What does Leptin do in regards to Puberty?

Answer 22

• Leptin: an adipostatic hormone (leptos = thin)
• decreased Leptin → increased fat mass
• Potentailly a facilitatory signal to influence timing of puberty?
• Supported by the fact that obese children have earlier onset of puberty
• 1kg weight gain → lowers age of menarche by 13 days

Question 23

What will Leptin Deficiency lead to?

Answer 23

Can be due to abnormal leptin hormone or Abnormal leptin receptor.

Sufferers are morbidly obese and don’t go through puberty (no trigger)

• Inject with leptin, to trim down and go through puberty like normal
• Very rare

Question 24

Leptin levels peak ___________ in boys

Answer 24

Leptin levels peak jsut prior to puberty in boys

Question 25

What is the current **Age of Menarche** and what is this dependent on?

Answer 25

* The **average age is getting younger, due to increasing weights** * Directly correlated with **body fatness** There's a wide **racial variation (body fatness)** * 11.5yrs US black (thicker women\> taller, stronger) * 12.3yrs US white * 12.8yrs UK Fallen in US by 0.34 in the past 25yrs

Question 26

How does body composition change inpuberty for males and females?

Answer 26

**Prepubertal male and female are the same in terms of lean, skeletal and fat mass** **_Puberty:_** * Lean and skeletal mass; **Males 1.5x more** then females * Fat mass; **Females 2x more** then males * Fat * Males: truncal * Females: generalised * There's increased **bone mineral density** in **both** with **peak bone mass achieved in early 20's**

Question 27

What makes you grow? Ie what are the **pubertal growth factors?**

Answer 27

Increased: * Sex steroids * Growth Hormone * IGF-I * insulin

Question 28

If a baby boy is born with a really small falalce, you consider?

Answer 28

1. Pituitary GH deficiency 2. Haven't gone through pre-natal puberty; and had big spike of testoserone/LH/FSH in utero \*\* don't assess boys for penile issues until 10-12yr as nothing happens till then!!

Question 29

SUmmary timeline of male and female puberty

Answer 29

Boys: \*also sperm prod and gynaecomastia occur 1. Increased testicular size ~11.5-12yr * Increase penile length ~11.5 * Scrotum enlargens and darkens 2. Pubic Hair after ~12yr * Axillary and facial hair later 3. Voice breaks ~14.5yr 4. Height Spurt Girls: 1. Breast budding starts~11yr 2. Height Development 3. Pubic hair begins ~6months later * ​​Axillary Hair later 4. Menarche