Lecture 24: Puberty

Question 1

What are the outcomes of puberty?

Answer 1

• Secondary sex characteristics appear and mature
• Adolescent growth spurt
• fertility is achieved
• Profound psychological changes

Question 2

How are the outcomes of puberty achieved directly or indirectly?

Answer 2

These changes result directly or indirectly from:

• Maturation of the Hypothalamic-pituitary Gonadotrophin unit
• Stimulation of the sex organs
• Secretion of sex steroids

Question 3

What is the normal start and progression of puberty?

Answer 3

Normal puberty starts at a normal time and progresses at a normal rate (~4 years)

• Central activation of the HP Gonodal axis
• Progressive sequential changes
• Appropriate rate 3-4 years

Question 4

What are the first signs of puberty in girls?

Answer 4

Girls first signs

• Breast development (Tanner stage 2)
• Then growth spurt

Question 5

What are the first signs of puberty in boys?

Answer 5

• Increased testicular enlargement
• > 3ml
• Growth spurt later

Question 6

What are the so called three puberties?

Answer 6

Fetal life: HPA axis turns on & sexual differentiation occurs

Infant: Minipuberty, HPA axis turns on a little and then turns off.

Teen: Regular puberty

Question 7

Describe the pubertal onset and sequence in girls:

Answer 7

Insert slide 8

Question 8

Describe the pubertal onset and sequence in boys:

Answer 8

Insert slide 9

Question 9

Define:

• Thelarche
• Pubarche
• Gonadarche
• Menarche
• Gynaecomastia

Answer 9

• Thelarche : Breast development
• Pubarche : Pubic hair development
• Gonadarche : Gonadal development
• Menarche : First menstural period
• Gynaecomastia : Breast development in boys

Question 10

Whats a better indicator of male development than pubic hair?

Answer 10

Testicular volume

+3ml = puberty, orchidometer

Question 11

What happens to penile growth?

Answer 11

Stops between 5-10 and after 18

Question 12

Write some notes on tanner stage breast development:

Answer 12

Stage 2: Elevation of breast, bud still attatched
Stage 3: Further elevation and areola but no separation or contour
Stage 4: Areola and papilla form a secondary mound above level of breast.
Stage 5: Areola recesses to the general contour of the breast

About shape and contour NOT SIZE

Question 13

Slide 18

Answer 13

slide 18

Question 14

Where in the Hypothalamus is GnRH released from?

Answer 14

GnRH : Median preoptic nucleus

Question 15

Describe the negative feedback loop of GnRH in females and so on:

Answer 15

GnRH (Hypo) -> FSH and LH -> (FSH acts on GCs to produce aromatase and Inhibin) (LH acts on Theca cells to produce Androgens) [Aromatase converts Androgens to estrogens)

Estrogen i.e estradiol negatively feedbacks to H&P
Inhibin negatively feedsback to pituitary
Progesterone produced from the later CL negatively feeds back to the H&P

Question 16

Describe the negative feedback loop of GnRH in males and so on:

Answer 16

GnRH (Hypo) -> FSH and LH -> (LH acts on leydig cells to produce testosterone) (FSH acts on sertoli cells to produce inhibin)

Testosterone feedsback negatively to the HYPOTHALAMUS

Inhibin feedsback negatively to the pituitary

Question 17

Describe the changes in LH and FSH secretion during puberty:

Answer 17

Early: Tonic phase increases, night pulses begins

Mid-puberty: Greater increase in tonic phase, Higher amplitude night pulses

Late puberty: Day and night pulses

Question 18

What is the gonadostat?

Answer 18

• Intrinsic CNS inhibitory system (enhances HPG negative feedback loops)
• Sex steroid dependent
• GABA appears to be the potent inhibitor of GnRH secretion

Question 19

Insert slife 28

Answer 19

thanks

Question 20

Describe the childhood to puberty transition:

Answer 20

• Gonadostat is turned off
• Increased pulsatile GnRH and LH/FSH secretion
• Increased sex steroid production
• Reduced sensitivity to negative feedback from sexy steroids

Question 21

What is kisspeptin? Where does it send neurons?

Answer 21

• Product of the kiss-1 gene
• Natural occuring ligand for GPR54
• Has neurons: Arcuate nucleus, periventricular nucleus, preoptic nucleus (GnRH cellbodies)

Question 22

Whats the evidence to suggest kisspeptin as a puberty trigger?

Answer 22

Evidence:

• GPR54 inactivation mutations leads to a failure to go into puberty
• Kisspeptin administration to prepubertal rats stimulates LH and ovulation
• KISS1 and GPR54 expression increased at the start of puberty
• The GPR54 receptor regulates GnRH secretion and or release from the hypothalamus

Question 23

What stimulates inhibin and what does it do?

Answer 23

• Inhibin release stimulates by FSH
• Negative feedback to FSH secretion

Produced by sertoli cells and GCs

Question 24

Whats the role of leptin in puberty?

Answer 24

• May be a facilitatory signal to influence timing of puberty
• Increased fat = increased leptin (adipostatic hormone) and obese children have earlier onset puberty
• Leptin levels peak just prior to onset of puberty in boyus
• Leptin deficient mice dont achieve puberty, but, administration of leptin induces puberty

Question 25

When does adrenarche occur? Whats its relation to puberty? What does it cause?

Answer 25

- Occurs in late childhood (8-10) - Increased adrenal production of androgens i.e DHEA - Temporal association with puberty, not a sign - Induces Pubarche, adult body odour, acne, oily skin

Question 26

Whats the age of menarche?

Answer 26

... Getting younger - Directly correlated with body fatness - Wide racial variations (body fatness)

Question 27

How does body composition relate to puberty?

Answer 27

Prepubertal male = female in terms of lean, skeletal and fat mass Puberty: - Lean mass, skeletal muscle mass (M 1.5x F) - Fat mass (F 2X M) - Fat: Males: Truncal, Females, generalised - Increased body mineral density in puberty with peak bone mass achieved in early 20s

Question 28

What are the pubertal growth factors?

Answer 28

- Increased sex steroids - Increased growth hormone - Increased IGF-1 - Increased insulin

Question 29

What categorizes someone into preocious puberty?

Answer 29

Boys: - < 8 y/o - Later growth spurt Girls: - Growth spurt - Tanner stage 2 (i.e signs of puberty) Both: - Indicates HPG turned on - FSH and LH measureable - Can do GnRH stimulation test

Question 30

What are possible pathologies of precocious puberty?

Answer 30

- Might be no pathology esp. in girls - BUT common in children with neurological problems/brain injury i.e epilepsy or CP Common pathologies - Hypothalamic hamartoma - CNS tumor The younger the male is the more likely of pathology

Question 31

What is the treatment and further investigation of precocious puberty?

Answer 31

- MRI (tumors) Meds - To preserve final height - Social indications The meds are very long acting GnRH agonists. Shuts down axis because axis requires pulsatile GnRH secretion to be active

Question 32

What does early breast development indicate and what are some possible causes?

Answer 32

Indicates exposure to estrogen (not necessarily puberty) Could be: - True central puberty (progressive, growth acc, bone age advances) - Benign premature thelarche (minimal development, not progressive) - Peripheral estrogen source i.e ovarian cyst or tumor - Exogenous estrogen (hormonal meds or essential oils)

Question 33

What does premature pubarche indicate and what are some causes?

Answer 33

Indicates androgen exposure Girls: - Premature adrenarche (no breast development) Boys: - Premature adrenarche (<3ml testis) - True puberty (>3ml testis, testosterone elevated) Or: - Abnormal secretion: Tumor, CAH - Exogenous: Meds, body building drugs

Question 34

What is late puberty?

Answer 34

>13 in girls, >14 in boys | - Usually is just exaggerated constitutional delay of growth and development (normal)

Question 35

What are some causes of late puberty?

Answer 35

Hypogonadotrophic hypogonadism - I.e pituitary malformation, pituitary damage, kallmann syndrome (cant smell) Primary hypogonadism - i.e turner syndrome, klinefelter syndrome, (LH and FSH will be high)