Sex Differentiation and Puberty

Question 1

List 3 measurements used to assess the adolescent growth spurt.

Answer 1

1 - Time of minimum growth velocity (the age immediately preceding the growth spurt).

2 - Peak height velocity (PHV - the highest rate of growth).

3 - Time of decreased growth velocity (the age immediately following the growth spurt).

Question 2

On average, when do boys experience the growth spurt relative to girls?

Answer 2

On average, boys experience the growth spurt two years later than girls.

Question 3

What is the difference in average height gain during puberty between boys and girls?

Answer 3

On average, boys gain 28cm, whereas girls gain 25cm during the growth spurt.

Question 4

List 5 physiological factors that are required for normal puberty.

Answer 4

Normal puberty needs:

1 - Normal XX or XY chromosomes.

2 - A normal hypothalamus.

3 - A normal pituitary.

4 - Normal ovarian / testicular function.

5 - Normal responsiveness of tissues to hormones.

Question 5

How does gonadotropin secretion change throughout the circadian rhythm in early puberty?

Answer 5

In early puberty, FSH and LH secretion is low throughout the day and becomes moderately pulsatile at night.

Question 6

How does gonadotropin secretion change throughout the circadian rhythm in mid-puberty?

Answer 6

• In mid-puberty, LH secretion is constant / non-pulsatile but is moderately increased from the basal level of secretion in earlier puberty.
• In mid-puberty, FSH secretion is still pulsatile at night, but the pulses are greater. Some lesser pulses also start to occur in the day.

Question 7

How does gonadotropin secretion change throughout the circadian rhythm in mid-puberty?

Answer 7

• In late puberty, LH secretion is constant / non-pulsatile but is significantly increased from the basal level of secretion in earlier puberty.
• In late puberty, FSH secretion is pulsatile throughout the day, and the pulses are greater.

Question 8

What is hypogonadotropic hypogonadism?

Answer 8

Hypogonadotropic hypogonadism is a condition in which there is a decrease in activity of the gonads due to a failure of secretion of gonadotropins.

Question 9

List 2 proteins that contribute to hypogonadotropic hypogonadism.

What is the function of these proteins?

Answer 9

1 - GPR54 (a receptor).

2 - Kisspeptin (a ligand for GPR54 secreted by KISS neurones).

• These proteins initiate gonadotropin secretion at puberty.

Question 10

What is the true / central precocious puberty?

How does it differ from precocious pseudopuberty?

Answer 10

• True / central precocious puberty is early onset puberty due to a defect (increased) in GnRH or gonadotropin secretion (GnRH-dependent).
• In contrast to precocious pseudopuberty, where the defect is further down, e.g. in the gonads, adrenal glands liver, etc (GnRH-independent).

Question 11

How is a differential diagnosis of true precocious puberty and precocious pseudopuberty carried out?

Answer 11

• In puberty, the dominating gonadotropin is LH.
• Therefore, with administration of GnRH, both LH and FSH will increase, but the LH:FSH ratio will be >1.
• If the patient suffers from true / central precocious puberty, the pituitary will hypersecrete FSH and LH in response to GnRH. The LH:FSH ratio will be significantly >1.
• If the patient suffers from precocious pseudopuberty, the pituitary will respond with a normal increase in secretion of FSH and LH in response to GnRH. The LH:FSH ratio will not be >1.

Question 12

How are the clinical signs of true precocious puberty different from that of precocious pseudopuberty?

Answer 12

• In true precocious puberty, the signs of early pubertal development are in agreement with other features of puberty, e.g. pubic hair growth, growth spurt etc.
• In precocious pseudopuberty, the signs of early pubertal development are in isolation, and are not in agreement with other features of puberty.
• This is because if the problem is central, then all peripheral structures will be affected because the hypersecreted FSH and LH will affect the whole circulation.

Question 13

List 3 causes of true precocious puberty.

Answer 13

Causes of true precocious puberty:

1 - CNS tumours.

2 - Developmental disorders.

3 - Encephalitis.

Question 14

List 3 causes of precocious pseudopuberty.

Answer 14

Causes of precocious pseudopuberty.

1 - Congenital adrenal hyperplasia.

2 - Non-central gonadotropin-secreting tumours, e.g. choriocarcinoma and chorioepithelioma.

3 - McCune-Albright syndrome.

Question 15

What is McCune-Albright syndrome?

Answer 15

• McCune–Albright syndrome is a genetic disorder affecting the bone, skin and endocrine systems.
• It is a mosaic disease caused by a mutation to the Gs alpha subunit.

Question 16

What is the difference between sex determination and sex differentiation?

Answer 16

• Sex determination is the initial formation of the gonads, which is controlled by the sex chromosomes.
• Sex differentiation is the influence of the gonadal steroids to influence secondary characteristics.

Question 17

What are Tanner stages?

What are Prader stages?

Answer 17

• Tanner stages is a staging system used to measure degree of pubertal development.
• Higher stages indicate stronger pubertal development.
• Prader stages is a staging system used to measure degree of virilisation in women.
• Higher stages indicate stronger virilisation.

Question 18

Which enzyme activates testosterone?

What is the product of activation of testosterone?

Answer 18

• 5 alpha-reductase activates testosterone.

- The product of activation is dihydrotestosterone (the most potent male hormone).

Question 19

What is SRD5A2 deficiency?

Answer 19

• SRD5A2 deficiency is a mutation in SRD5A2, which encodes 5 alpha-reductase 2.
• This results in a decrease in activated testosterone (dihydrotestosterone), causing feminisation.

Question 20

What is AIS?

Answer 20

• AIS is androgen insensitivity syndrome.
• CAIS is complete androgen insensitivity syndrome, and is caused by an X-linked genetic defect in the androgen receptor.
• PAIS is partial androgen insensitivity syndrome, and is caused by the same thing as CAIS.
• It is only clinically significant in genetic males (as in females the androgens are converted into other steroid hormones anyway).