sexual differentiation in puberty

Question 1

What is the definition of puberty?

Answer 1

the physiological, morphological, and behavioural changes as the gonads switch from infantile to adult forms.

Question 2

What is the definitive sign of the start of puberty for boys and girls?

Answer 2

Females- first menstrual bless

Males- first ejaculation (often nocturnal)

Question 3

Three stages of adolescent growth spurt

Answer 3

1. The ‘age at take-off’ is the period of minimum growth velocity that immediately precedes the growth spurt
2. Peak height velocity
3. Time of decreased growth velocity and cessation of growth which occurs at the fusion of the epiphysis

Question 4

Effect of LH in males during puberty

Answer 4

LH will act at the Leydig cells in males, re-initiating testosterone release from these cells they will have been dormant since their function in-utero

Question 5

Effect of LH in females during puberty

Answer 5

Act at the Theca cells in females, causing a release of androgens that will be aromatased to oestrogen in the Granulosa cells

Question 6

Effect of FSH in males and females during puberty

Answer 6

• FSH will act at Sertoli cells in males and Granulosa cells in females and is essential for gamete maturation

Question 7

What is the role of kisspeptin in puberty?

Answer 7

GnRH release is thought to occur in response to the release of kisspeptin and neurokinin

These two factors are essential for the initiation of gonadotrophin secretion, and without them puberty will not occur

Activating mutations in these factors may also result in precocious puberty.

Loss of function and mutation in GPR54 gene causes a failure to progress through puberty in men due to Hypogonadotropic hypogonadism

Kisspeptin is a ligand for the G protein coupled receptor GPR54 which is expressed in hypothalamic GnRH neurons

Kisspeptin-GPR54 is essential for the initiation of the gonadotropin secretion at puberty

Question 8

What is precocious puberty

Answer 8

onset of secondary sexual characteristics before 8 in girls and 9 in boys

Question 9

what is delayed puberty

Answer 9

absence of secondary sexual characteristics by 13 in girls and 14 in boys

Question 10

What is true precocious puberty

Answer 10

the entire HPG axis is activated, indicated by pulsatile GnRH release

This has a relatively high incidence, and is much more common in females

The majority of cases of true precocious puberty are idiopathic in females, however in males it is generally a key indication of some form of brain tumour

Question 11

precocious pseudopuberty

Answer 11

the events are GnRH independent (not in hypothalamus)

This will generally occur due to increased androgen secretion, most commonly as a result of CAH. However, it may be due to a gonadotrophin secreting tumour

Many tumours will secrete hCG, which will act at LH receptors to stimulate the gonads resulting in sex hormone action

Question 12

How do you differentiate between true precocious puberty and precocious pseudopuberty?

Answer 12

distinguished by GnRH test

In true precocious puberty, stimulation with GnRH will increase LH and FSH to pubertal range, in an LH:FSH ratio >1

In precocious pseudopuberty, stimulation with GnRH will only increase LH and FSH to prepubertal levels, in an LH:FSH <1

Question 13

what is the definition of sex

Answer 13

Biological and refers to primary and secondary sexual characteristics

Is determined by chromosomes, genes and hormones and can be changed (transgender)

Question 14

what is the definition of gender

Answer 14

psychological, social entity that is subjective to cultural norms

Is probably instilled from a young age by society

Question 15

what is CAH (congenital adrenal hyperplasia)

Answer 15

block in adrenal steroidogensis affecting glucocorticoid synthesis

21-hydroxylase deficiency is most common cause - block in mineralocorticoid production so no cortisol or aldosterone

results in life threatening crisis due to adrenal crisis due to lack of salt production and blood pressure regulation

17OHP is the marker steroid which increases in CAH as it occurs before the block

male hormones can still be made so females are virilised to 46 XX DSD - male genetalia

females are more likely to survive as unusual genitals are recognised at birth, but not in males so they die of adrenal crisis

Question 16

CAH due to 17-alpha-hydroxylase

Answer 16

17α-hydroxylase is later in the steroid pathway of the adrenal glands
enabling mineralocorticoid synthesis,
but blocking conversion to glucocorticoid and androgen precursors

In this, the reverse occurs and there is 46 XY DSD and the male gains the appearance of female external genitalia

There will be mineralocorticoid excess, glucocorticoid deficiency, and androgen deficiency

Question 17

5-alpha-reductase type 2 deficiency

Answer 17

block the conversion of testosterone to DHT, this will also cause 46 XY DSD

In neonatal and pre-pubertal life these individuals will appear female, however at puberty due to the influence of LH increasing the production of testosterone by the Leydig cells they will develop a male phenotype due to the converting activity of 5α-reductase type 1

Genitalia at birth will be ambiguous, with a small hypospadic phallus and blind vaginal pouch. Testes will be normal, but undescended

sex assignment- better to raise as male as they will go on to develop male phenotypes

Question 18

androgen insensitivity syndrome

Answer 18

46 XY DSD.

This is caused by mutations in the androgen receptor, meaning that there is no response to the androgens present and female external genitalia will develop

Due to production of AMH, there will be paramesonephric degeneration and no female internal genitalia, but male internal genitalia will be present dependent on the type of mutation

These individuals will have very high testosterone and DHT levels due to a lack of negative feedback as the receptors are not expressed

Patients will have female external genitalia and breasts with a blind ending vagina, they will typically have little pubic and axillary hair, and present with primary amenorrhea