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Reproduction (Physiology 2) > Hypothalamic/Pituitary/Gonadal Axis II > Flashcards

Hypothalamic/Pituitary/Gonadal Axis II Flashcards

1
Q

What are the characteristics of puberty?

A

Transition from non-reproductive to reproductive state
Gonads produce mature gametes
Secondary characteristics develop (primary (genitalia) are present at birth)
Profound physiological changes
Profound psychological changes

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2
Q

What are the mature gametes produced by the gonads?

A

Testes 🡪 spermatozoa

Ovaries 🡪 oocytes (born with full oocyte number which develop at puberty)

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3
Q

What are the 2 major endocrine events of puberty?

A

Adrenarche

Gonadarche

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4
Q

What is adrenarche?

A

Adrenarche is the release / secretion of adrenal androgens resulting in pubarche

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5
Q

What is pubarche?

A

Pubarche is the growth of pubic and axillary hair as well as an increase in height

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6
Q

What is gonadarche?

A

Gonadarche is the switching on of the HPG axis followed by LH/FSH secretion

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7
Q

What is the significance of gonadarche?

A

This is responsible for:
LH: steroid synthesis in the gonads causing secondary sex characteristics

FSH: growth of testis (male) and folliculogenesis and steroid synthesis in females

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8
Q

When do adrenarche and gonadarche occur?

A

Adrenarche and Gonadarche culminate in puberty and are independently regulated

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9
Q

What occurs in the foetal adrenal gland?

A

During foetal development the foetal adrenal gland secretes adrenal androgens from the foetal zone

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10
Q

How does remodelling alter the foetal zone?

A

During remodelling the foetal zone begins to shrink and expansion and growth of the definitive zone occurs
No change in other adrenal steroids

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11
Q

What is the role of the definitive zone?

A

The definitive zone starts to release the adrenal androgens responsible for adrenarche

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12
Q

Name the 2 main androgens responsible for adrenarche?

A

The 2 main ones are:

  • Dehydro-epiandrosterone (DHEA)
  • Dehydro-epiandrosterone sulphate (DHEAS)
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13
Q

When are the adrenarche androgens mainly released?

A

Gradual increase 6 🡪 15 years
20-fold increase peaking at ̴20-25 years
Declines thereafter

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14
Q

Where in the adrenal gland are DHA and DHEAS secreted?

A

DHA and DHEAS are secreted from zona reticularis of adrenal cortex

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15
Q

What triggers the onset of adrenarche?

A

No known mechanism for trigger of adrenarche

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16
Q

What occurs during pubarche?

A

Appearance of pubic / axillary hair resulting from adrenal androgen secretion

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17
Q

When does pubarche occur in individuals?

A

If before 8 years (girls) or 9 years (boys)

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18
Q

What is precocious puberty?

A

PRECOCIOUS = early puberty

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19
Q

What are the changes associated with pubarche?

A

Associated with:
↑ sebum production = acne
Acne may also be due to infection, abnormal keratinization of the skin

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20
Q

At what age does gonadarche occur?

A

Several years after adrenarche (typically ~11 yrs of age)

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21
Q

What occurs during gonadarche?

A

Reactivation of hypothalamic GnRH secretion

Activation of gonadal steroid production 🡪 production of viable gametes and ability to reproduce

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22
Q

Why is reactivation of the HPG axis required?

A

During foetal development (16th week of gestation) the HPG axis is activated - required for sexual differentiation
Shortly after birth the HPG axis is deactivated

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23
Q

When is the HPG axis initiated?

A

HPG axis is first activated at 16th gestational week

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24
Q

Where is GnRH secreted from?

A

GnRH is synthesised & secreted by specialist hypothalamic centres- GnRH neurones

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25
Q

At what age is GnRH secreted?

A

Pulsatile GnRH secretion in foetus until 1-2 years postnatally when ceases
Re-activation at ~11 years
GnRH neurones ‘restrained’ during postnatal period 🡪 10 years or more
At puberty a gradual rise in pulsatile release of GnRH

26
Q

What causes the onset of puberty?

A

Clear that it is maturational event within the CNS
- Inherent (genetic) maturation of 1000-3000 GnRH
synthesising neurones
- Environmental/genetic factors
- Body fat/nutrition
- Kisspeptin

27
Q

How does Anorexia Nervosa / intensive physical training affect puberty?

A

Reduced response to GnRH
↓gonadotrophin levels
Amenorrhea
Restored when nourished / exercise stopped

28
Q

How does body fat / weight effect onset of puberty?

A

Certain % fat:body weight necessary for menarche (first menstrual cycle) (17%) & required (22%) to maintain female reproductive ability

29
Q

Explain the link between nutrition and puberty

A

Regulation of puberty can be mediated via leptin (satiety factor) and Ghrelin (appetite stimulating hormone)
These two hormones feed into the hypothalamus which regulates the release of kisspeptin.
Release of kisspeptin regulates the onset of puberty

30
Q

What does the inactivation of Kispeptin gene/ KISS1R mutations cause?

A
  • Hypogonadism
  • Failure to enter puberty
  • Hypogonadotrophism
  • Hypogonadism
31
Q

What is the effects of activating KISS1R mutations?

A

Precocious puberty

32
Q

What is consonance?

A

Smooth ordered progression of changes

Order of pubertal changes is uniform

33
Q

When do the physical changes of puberty take place?

A

Age of onset, pace & duration of changes
Wide inter-individual differences
Average age of menarche onset (UK) = 12.5 years

34
Q

What are the average ages of pubertal development in girls and boys?

A

Differences in age of pubertal development .

All girls are 12.75 years and all boys are 14.75 years in these drawings

35
Q

What are the physical characteristics of puberty?

A

Looks at the following:

i) Breasts
ii) Pubic & axillary hair growth
iii) Male genitalia

36
Q

What hormone is responsible for the pubertal changes in females?

A

In response to oestrogen the cellular makeup of the uterus, vagina and the cervix change and secretory activity begins

37
Q

What are the physical changes that occur during puberty in females?

A
  • Breasts enlarge: thelarche – first outward sign of E2
    (oestrogen) activity
  • Pubic/axillary hair
  • Uterus enlarges, cytology changes, secretions in
    response to E2
  • Uterine tubes, Vagina, Cervical
    changes
  • Height: earlier onset than boys, peak height velocity
    (PHV) = 9 cm/y, reached at 12 yrs
  • Body shape
  • HPG axis: increase in ovarian size and follicular growth
  • Menarche: not equated with onset of fertility
  • Fertility: in 1st year ~80% menstrual cycles anovulatory,
    irregular cycles
38
Q

What are the physical changes associated with male puberty?

A
  • External genitalia: increase in testicular volume >4 ml,
    growth of penis, scrotum, scrotal skin changes
  • Vas deferens: lumen increases
  • Seminal vesicles & prostate
  • Facial/body hair
  • Pubic / axillary hair
  • Larynx – androgens 🡪 enlarge larynx, Adams apple
    (projection of thyroid cartilage), voice deepens
  • Height: PHV = 10.3 cm/y reached at 14 yrs
  • Body shape
  • Onset of fertility: testosterone from Leydig cells
    stimulates meiosis & spermatogenesis in Sertoli cells
    boys fertile at the beginning of puberty
39
Q

How is testicular volume measured?

A

Prader orchidometer numbers represent the volume in millimeters
10th, 50th, 90th centiles of testicular size in boys at different ages

40
Q

What causes growth spurt?

A

Complex interaction between Growth hormone and Oestrogen (boys and girls)
Earlier in girls – approx. 2 years

41
Q

How does oestrogen cause a growth spurt to occur?

A

Biphasic effect of oestrogen on epiphyseal growth
Low levels 🡪 linear growth & bone maturation
High levels 🡪 epiphyseal (bone) fusion: marks end of bone growth

42
Q

What are pilosebaceous units (PSUs)?

A

The structure consisting of hair, hair follicle, arrector pili muscle and sebaceous gland in the skin

43
Q

What are the 2 main types of PSUs in the skin?

A

2 main types of pilosebaceous units in the skin :

  • Sebaceous PSU
  • Villous PSU
44
Q

What effect do androgens have on the sebaceous PSUs?

A

Androgens result in an increase in sebum production in sebaceous PSU which with infection can cause acne

45
Q

What is the role of Vellous PSUs?

A

Vilous PSU are responsible for hair growth. Androgens modulate the differentiation of the vilous PSU into the Terminal PSU and APO-PSUs

46
Q

What are the roles of the differentiated vellous PSUs?

A

Terminal PSU - responsible for beard growth

APO-PSU - responsible for pubic and axillary hair

47
Q

What psychological changes occur during puberty?

A

Increasing need for independence
Increasing sexual awareness/interest
Development of sexual personality

Later maturation = better adjustment

48
Q

How is Precocious Sexual development clinically defined?

A

Development of any secondary sexual characteristics:
before the age of 8 in girls
before the age of 9-10 in boys

Precocious puberty is when pubertal changes are early BUT in consonance
Its v rare

49
Q

What are the 2 methods of premature activation of the HPG axis?

A
  1. Gonadotrophin-dependent (or central) precocious
    puberty
  2. Gonadotrophin-independent precocious puberty
50
Q

Describe Gonadotrophin-dependent precocious puberty

A

consonance
Excess GnRH secretion - idiopathic or secondary
Excess gonadotrophin secretion - pituitary tumour

51
Q

Outline the causes of gonadotrophin-indepndent precocious puberty

A

Loss of consonance
Testotoxicosis - activating mutation of LH receptor
Sex steroid secreting tumour or exogenous steroids

52
Q

What is the McCune Albright Syndrome?

A

Mutations in the GNAS1 gene responsible for G𝛼S subunit of the G protein causing the activation of all the pathways requiring the G protein

Hyperactivity of signalling pathways & over-production of hormones

53
Q

What are some of the characteristic symptoms fo McCune Albright syndrome?

A

Fibrous dysplasia and Café au lait skin pigmentation are the result of G protein coupled signalling pathways

54
Q

What classes as pubertal delay?

A

Absence of secondary sexual maturation by 13yrs in girls

(or absence of menarche by 18yr) or 14yrs in boys

55
Q

What are the 3 main causes of pubertal delay?

A
  1. Constitutional delay
  2. Hypogonadotrophic hypogonadism
  3. Hypergonadotrophic hypogonadism
56
Q

What is constitutional delay?

A

Affecting both growth and puberty
Approx. 90% of all pubertal delay cases
~10X more common in boys
Secondary to chronic illness e.g., diabetes, cystic fibrosis

57
Q

What is Hypogonadotrophic hypogonadism?

A

(low LH and FSH)
Kallman’s syndrome (X-linked KAL1 gene, impaired GnRH migration),
Other mutations causing defects in GnRH production

58
Q

What is Hypergonadotrophic hypogonadism?

A

(high LH and FSH)
Gonadal dysgenesis and low sex steroid levels:
gonadal dysgenesis with normal karyotype, viral e.g. mumps

59
Q

What is Klinefelter’s syndrome ?

A

Gonadal dysgenesis resulting from abnormal karotype

XXY or variants
1 : 500 males
Characterised by feminine features: breast development, height increase
External genitalia remain male but may have pubertal issues

60
Q

What is Turners Syndrome?

A

XO
1 : 3000 girls

2 classic symptoms of Turners:
Being shorter than normal
Underdeveloped or “streak” ovaries

Reproduction (Physiology 2) (12 decks)

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