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Repro > HPG 2 > Flashcards

HPG 2 Flashcards

1
Q

Define puberty

A

The transition from the non-reproductive to the reproductive state

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2
Q

What happens (briefly) in puberty?

A

1) Gonads produce mature gametes - testes make spermatozoa and ovaries develop oocytes
2) Breast development in females, increased testicular volume in males
3) Secondary characteristics develop
4) Physiological changes such as hair patterning, height, and actual body shape, along with some psychological changes

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3
Q

What are the two endocrine events that occur during puberty?

A

1) Adrenarche

2) Gonadarche

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4
Q

What is adrenarche?

A

The change in adrenal androgen secretion due to cellular remodelling of the adrenal glands.

DHEA and DHEAS levels change, with a gradual increase in their serum levels starting from the age of 6-15, to a 20-fold increase peaking at 20-25 years of age. It declines thereafter. It is secreted from the zona reticularis of the adrenal cortex.

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5
Q

What is gonadarche?

A
  • LH leads to steroid synthesis and the development of secondary characteristics
  • FSH stimulates the growth of testes in males and steroid synthesis and follicular genesis in females
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6
Q

What does adrenarche cause?

A

Pubarche - which is the appearance of pubic/axillary hair resulting from adrenal androgen secretion

Increased sebum production (acne)

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7
Q

What else (apart from increased sebum) can cause acne?

A

Infection

Abnormal keratinisation

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8
Q

Describe gonadarche

A

Occurs several years after adrenarche (11 y/o)

Reactivation of the HPG (after foetal development)

Activation of gonadal steroid production, leading to the production of viable gametes and ability to reproduce

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9
Q

Describe GnRH

A
  • synthesised and secreted by specialist hypothalamic centres (the GnRH neurons)
  • HPG axis is activated in the 16th gestational week, and the pulsatile GnRH secretion in the foetus occurs until 1-2 years postnatally, and then they are ‘restrained’ for about 10 years or more
  • at puberty there is a gradual rise in the pulsatile release of GnRH
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10
Q

What changes in the pattern of LH secretion occur during puberty?

A

Early to mid-puberty: nocturnal rise of LH secretion, after which the rise is normalised throughout the 24 hour period

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11
Q

What stimulates the onset of puberty?

A

We do not have a definitive answer

  • Clear that it is a maturational event within the CNS
  • Environmental factors play a role
  • The epigenome also has a role to play
  • Body fat/nutrition: studies have shown a link between the onset and regulation of puberty and body fat and nutrition
  • Kisspeptin is the gatekeeper of puberty
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12
Q

How are nutrition and body fat linked to puberty?

A

There is a known link between fat metabolism and reproduction (PCOS causes metabolic dysfunction)

Also, in people with anorexia/athletes, it is found that they have:

  • a reduced response to GnRH
  • decreased gonadotrophin levels
  • amenorrhea

which is restored when they are nourished/stop training

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13
Q

What can inactivating mutations of KISS1R lead to?

A
  • hypogonadism
  • failure to enter puberty
  • hypogonadotropic hypogonadism
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14
Q

What can activating mutations of KISS1R lead to?

A
  • precocious puberty
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15
Q

What is consonance?

A

The smooth, ordered progression of changes through puberty

The age of onset/pace/duration of changes will vary between individuals, but the order they occur in will remain the same

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16
Q

What are the Tanner stages of puberty?

A

A scale of physical measurements of development

There are 5 stages, and 3 parameters:

  • breasts in females
  • pubic and axillary hair growth
  • testicular volume and penile length in males
17
Q

Describe the physical changes in girls during puberty?

A
  • Breasts enlarge (thelarche: the first outward sign of oestrogen activity)
  • Pubic/axillary hair
  • Uterus enlarges, cytology changes, secretions in response to oestrogen
  • Uterine tubes
  • Vagina
  • Cervical changes
  • Growth in height, earlier onset than in boys
  • Changes in body shape
  • The reactivation of the HPG axis, which brings an increase in ovarian size and follicular growth
  • Onset of menarche, not equated with onset of fertility. Most women are not fertile after their first period because the HPG axis still has to go through that process of follicle growth and recruitment.
  • Usually fertility is attained after a year. 80% of the cycles are anovulatory or irregular
18
Q

Describe the physical changes in boys during puberty?

A
  • External genitalia: increase in testicular volume, growth of penis, scrotum, scrotal skin changes
  • Vas deferens lumen increases
  • Seminal vesicles and prostate secretions begin
  • Growth of facial and body hair
  • Pubic and axillary hair
  • The larynx and adams apple enlage
  • Voice deepens
  • Increase in height
  • Change in body shape
  • Onset of fertility: as soon as boys hit puberty they become fertile
19
Q

Describe the growth spurt during puberty

A
  • Complex interaction that involves growth hormone and oestrogen (in both boys and girls)
  • Occurs earlier in girls (approx. 2 years)

This growth spurt is a biphasic effect of oestrogen on bone growth. It starts with low levels of oestrogen, which is responsible for the linear bone growth and bone maturation.

And then, this is followed by high levels of oestrogen that are responsible for bone fusion. Bone fusion marks the end of bone growth

20
Q

Describe the effect of androgens on the differentiation of pilosebaceous units (PSUs)?

A
  • Sebaceous PSU

Androgens result in the increased sebum production in the sebaceous PSUs. This results in the increased presence of acne that you see during puberty.

  • Vellous PSU

Androgens result in the differentiation of these PSUs into terminal PSUs which are responsible for beard growth. The APO-PSUs are responsible for pubic and axillary hair.

21
Q

What are some psychological changes that occur during puberty?

A

1) An increasing need for independence
2) Increasing sexual awareness and interest
3) Development of sexual personality

The later the physical maturation, the better, as it reduces the chances of the disconnect between the physical and psychological changes.

22
Q

Define precocious sexual development

A

It is the development of any secondary sexual characteristics before the age of 8 in girls and the ages of 9-10 in boys.

Precocious puberty is when pubertal changes (ie. the reawakening of the HPG axis) occur too early , but still in consonance.

23
Q

What are two ways in which the premature re-awakening of the HPG axis can occur?

A

1) Gonadotrophin-dependent precocious puberty - consonance

Puberty as a result of something going wrong with the gonadotrophins. This comes with excess GnRH secretion, and excess gonadotrophin secretion. There are cases where pituitary conditions e.g. pituitary tumours could result in precocious puberty.

2) Gonadotrophin-independent precocious puberty - loss of consonance

FSH, LH, GnRH secreted and functioning normally, but the gonads are actually synthesising steroids at an abnormally high amount, resulting in gonadal maturation too early. In a case of testotoxicosis, you have an activating mutation of the LH receptor in the testes, so as a result the pathways through which the Leydig and Sertoli cells mediate spermatogenesis are activated long before the onset of puberty. You only have maturation of the genitalia, but none of the other secondary sexual characteristics that come with puberty (e.g. tanner stages).

24
Q

How would McCune Albright syndrome cause precocious puberty?

A

McCune Albright Syndrome is a result of an α G-subunit activating mutation. This is the hyperactivity of this signalling pathway, thus it will over-produce the hormones that work by this pathway.

LH and FSH work through this pathway, so we would get their overproduction, leading to precocious puberty.

25
Q

Define pubertal delay?

A

It is the absence of secondary sexual maturation by 13 years of age in girls (or absence of menarche by 18 years), or 14 years in boys.

26
Q

What are three ways in which the awakening of the HPG axis is delayed?

A
  1. Constitutional delay
    - affecting growth and puberty
    - 10 times more common in boys
    - secondary to chronic illness (eg. diabetes, cystic fibrosis)
  2. Hypogonadotrophic hypogonadism (low LH and FSH)
    - Kallman’s Syndrome (X-linked KAL1 gene, impaired GnRH migration)
    - other mutations causing defects in GnRH production
  3. Hypergonadotrophic hypogonadism (high LH and FSH)
    - gonadal dysgenesis and low sex steroid levels (can occur with normal karyotype, via viral infection eg. mumps)
27
Q

What are some chromosomal abnormalities that can cause gonadal dysgenesis?

A
  • Klinefelter’s Syndrome (an extra X chromosome, XXY)
    would have male genitalia, but also wide hips, long arms and legs, and some breast development
  • Turner’s Syndrome (missing an X chromosome, XO)
    are shorter than usual, have underdeveloped or ‘streak’ ovaries
28
Q

Where are DHEAS and DHEA released from?

A

The zona reticularis of the adrenal cortex

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