36 Hormonal control of pubertal development

Question 1

Puberty is the result of maturation of which 3 systems?

Answer 1

Adrenarche: Adrenal gland
Gonadarche: Gonads
GH-IGF axis

Question 2

Describe the changes in the hypothalamic-pituitary-gonadal axis from fetal period to puberty.

Answer 2

1. Fetal life: functional (in male, androgen from fetal testis drives sexual differentiation)
2. Early infancy (few months after birth): removal of placental estrogen/progesterone > FSH and LH levels increase abruptly
3. Period of restraint: activity of the axis is suppressed to low level during childhood (1-years old)

Mechanism of restraint:

1. Hypothalamic-pituitary unit becomes highly sensitive to negative feedback inhibition by gonadal sex steroids > fall in FSH and LH
2. CNS inhibitory mechanism: GABAergic inhibitory neurons (GABA: inhibitory NT) > suppress GnRH synthesis and pulsatile secretion
3. Puberty
   - removal of intrinsic CNS inhibition > reactivate the GnRH pulse generator
   - first evidence: nocturnal rise in LH
   - decrease sensitivity of hypothalamic-pituitary unit to negative feedback by gonadal sex steroids

Question 3

The dominant mechanism responsible for initiating pubertal development is?

Answer 3

The removal of intrinsic CNS inhibition (by GABAerigc inhibitory neurons that suppress GnRH synthesis and secretion)

Question 4

The reactivation of the hypothalamic-pituitary-gonadal axis is augmented by?

Answer 4

Stimulatory NT like kisspeptins, neurokinin B, glutamate and other factors like neurotrophic factors, growth peptides etc.

Question 5

Describe the changes in pattern of serum gonadotropin levels (LH/FSH) ratio during postnatal life in the human female. (from before puberty to menopause)
Explain.

Answer 5

1. Before puberty: FSH > LH , esp in females
   Prepubertal boys have smaller readily releasable pool of pituitary FSH than girls, probably related to higher inhibin B secretion from the testis
2. Puberty: LH > FSH, as pituitary builds up a larger reserve of LH primed by the higher GnRH pulse frequency

LH pulsatile secretion increases during sleep

3. Reproductive years (after puberty) : LH secretion > FSH secretion + positive feedback response to estrogen; greater surge in LH induces ovulation
4. Menopause: cyclic changes disappear, gonadotrophin secretion increases due to the fall in gonadal feedback with a greater rise in FSH levels > LH

Question 6

Which of the following are true about kisspeptin-GPR54?

A. It has capacity to inhibit tumour metastasis
B. They bind to KISS1R receptor located within the nucleus of GnRH secreting neurons
C. They contribute to the pubertal resurgence of pulsatile GnRH release
D. Loss of function mutations of KISS1 and KISS1R are associated with hypergonadotropic/ hypergonadism in humans
E: Gain of function of KISS1R may cause GnRH-dependent central precocious puberty

Answer 6

All except B and D

B: on the surface of GnRH secreting neurons

D: hypogonadism!

Question 7

What is the normal sequence of events in pubertal development in girls?
(4 steps)

Answer 7

Thelarche, pubarche, pubertal growth spurt, and finally menarche.

(TPSM) (too painful SM)
In the first 1-2 years following menarche, the menstrual cycles are mostly irregular and do not exhibit a mean cycle length of 28 days.

Question 8

Adrenarche occurs before gonadarche.

T/F?

Answer 8

True, adrenarche begins 2 years before gonadarche

Adrenarche: Not accompanied by an increased in ACTH secretion, although the presence of ACTH is required

Question 9

Which of the following are false about adrenarche?
A: Adrenarche is a prerequisite for puberty to occur, and it affects the age of gonadarche.

B: Adrenarche is not accompanied by an increased in ACTH secretion, although the presence of ACTH is required

C: Maturation of adrenal cortex associated with increased secretion of adrenal androgens (DHEAS, androstenedione) leads to androgen-dependent changes that occur during pubertal development: growth of pubic and axillary hair, sebaceous gland secretion

D: Increase in DHEAS causes the proliferation of zona reticularis of adrenal gland

Answer 9

A and D

A: false
D: Increase in DHEAS causes the proliferation of zona fasciculata of adrenal gland

Question 10

True/ False?
Gonadarche:
Male: first indicated by increase in testicular volume
Female: first indicated by breast development (thelarche)

Answer 10

True

Question 11

Which of the body changes are caused by increase in androgen secretion?
A. closure of epiphyseal plate
B. deepening of voice
C. Axillary, pubic and body hair growth
D. increased activity and secretion of sebaceous gland
E. Growth and maturation of genitalia, reproductive tract and accessory sex glands
F. Pubertal growth spurt

Answer 11

All of the above

A. but mainly by estrogen
D. also with GH/IGF
E: only in males
F: mainly by estrogen, also with GH/IGF-1, thyroid hormones

Question 12

What is the normal sequence of events in pubertal development in male?
(5 steps)

Answer 12

testicular growth > puberache > penile growth > pubertal growth spurt > spermarche
(TPPSS) (vs TPSM)

Question 13

Which of the following are involved in primary disorders of gonad > elevated gonadotropin levels (hypergonadotropic-hypogonadism) ?

A. Turner's Syndrome
B. Kallmann's Syndrome
C. Klinfelter's Syndrome
D. Bilateral anorchia 
E. Chemotherapy
F. Gonadal dysgenesis

Answer 13

All except B

Secondary disorders of hypothalamic-pituitary unit with low gonadotropin levels (hypogonadotropic-hypogonadism)

1. Kallmann’s syndrome (GnRH neurons migration > less stimulation from above)
2. CNS tumour/ irradiation