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Science of Reproduction > Puberty > Flashcards

Puberty Flashcards

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1
Q

What is puberty?

A

A series of complex developmental changes leading to somatic and sexual maturation

Profound physiological, psychological and physical changes

Reproductive perspective: goal to produce mature gametes:

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2
Q

What are the major physiological changes that occur during puberty?

A

Testes 🡪 spermatozoa
Ovaries 🡪 oocyte

Breast development in females
Increased testicular volume in males

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3
Q

What are the 2 endocrine events of puberty?

A
  • adrenarche

- gonadarche

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4
Q

What changes occur in adrenarche?

A

Growth of pubic hair, axillary hair

Growth in height

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5
Q

What are the roles of LH during gonadarche?

A

steroid synthesis –> development of secondary sex characteristics

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6
Q

What are the roles of FSH in gonadarche?

A

Growth of testis (male)/steroid synthesis/folliculogenesis (female)

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7
Q

When does adrenarche occur?

A

First endocrine process of puberty

Occurs ~6-8 years

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8
Q

What are the signs of adrenarche?

A

Characterised by (re-)instigation of adrenal androgen secretion

  • DHEA
  • DHEA-S

No change in cortisol/other adrenal hormones - not a global activation of HPA axis

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9
Q

Where are DHEA/DHEAS secreted from during adrenarche?

A

Androgen secretion is from zona reticularis

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10
Q

What causes the release of DHEA/DHEAS from the adrenal cortex?

A

Result of inherent maturation of cellular compartments of adrenal cortex.

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11
Q

When does DHEA/S secretion begin?

A

Surge from around ages 6-8, Peak at mid 20s and then a decline.

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12
Q

Describe the maturation of the adrenal cortex causing onset of adrenarche

A

Remodelling of adrenal cortex occurs; causes secretion of androgens

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13
Q

What are the 2 zones of the fetal adrenal cortex?

A

Fetal adrenal gland consist of 2 zones:

  • Foetal zone
  • Definitive zone
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14
Q

How does adrenarche stop?

A

Initially foetal zone responsible for DHEA/S production but evolution causes shrinkage of foetal zone (↓DHEA/s)

Definitive zone enlarges and differentiates into zona glomerulosa and zona fasciculata (DHEA/S production stopped)

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15
Q

How are adrenal androgens reactivated in the zona reticularis?

A

Focal islands of zona reticularis tissue which expand and form a continuous and functional ZR layer ~6 adrenal androgens are reactivated - beginning of adrenarche (↑DHEA/S)

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16
Q

Outline the formation of DHEA/S

A

Cholesterol precursor of steroids
Converted into progenolone via CYP11A

CYP17 and Lyse 17,20 converts into DHEA/S

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17
Q

How does CYP protein expression differ during adrenarche?

A

CYP11 and CYP17 expression upregulated in individuals undergoing adrenarche compared to at infancy

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18
Q

What is the role of the 3bHSD enzyme?

A

3bHSD responsible for converting pregnenolone and DHEA/S into mineralocorticoids and glucocorticoids (cortisol ACTH etc.)

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19
Q

Describe the expression of 3bHSD during adrenarche

A

During adrenarche 3bHSD expression is switched off to ensure all Pregnenolone, cholesterol and DHEA/S is committed to adrenarche

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20
Q

What are the functipns of DHEA/S?

A

Metabolism within peripheral tissue - production of DHT

Drives maturation of hair
follicles required for growth of pubic and auxiliary hair.

Also aids prostate secretions

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21
Q

What is the effect of dexamethasone on adrenarche?

A

Dexamethasone suppresses adrenal androgen production - reduced ACTH

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22
Q

How is adrenarche stimulation affected in children with ACTHr mutations?

A

Children with ACTHr mutations fail to undergo adrenarche.
But they have no change in ACTH/cortisol during adrenarche

Divergent mechanisms for cortisol and androgen production at adrenarche?

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23
Q

What is POMC?

A

Proopiomelanocortin
Proximal 18 AA region that positively regulated adrenal androgen production
- no studies show POMC is responsible for adrenacrhe

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24
Q

What evidence supports the idea POMC-related peptides may affect adrenarche?

A

b-lipotrophin and b-endorphin plasma levels correlate with increased DHEA/S at adrenarche

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25
Q

What controls the onset and regulation of adrenarche?

A

No conclusive mechanism for control of adrenarche

26
Q

What is gonadarche?

A

(Re-)Activation of HPG axis

27
Q

When does gonadarche occur?

A

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

28
Q

What drives gonadarche?

A

Driven by hypothalamic GnRH & pituitary gonadotrophins.

Puberty depends on reactivation of GnRH release

29
Q

When is the HPG axis first initiated?

A

16th gestational week activation of HPG axis.

Pulsatile GnRH secretion in foetus and 1-2 years postnatal increased.

30
Q

How does the HPG axis become quiescent?

A

Neurones ‘restrained’ during postnatal period 🡪 10 years or more

31
Q

When does GnRH release begin to increase again?

A

At puberty a gradual rise in pulsatile release- around 1 year before breast budding observed

32
Q

How can GnRH levels be measured?

A

Serum levels of LH used as a measure of GnRH

33
Q

Describe the different levels of GnRH secreted throughout different pubertal phases

A

Early-mid puberty
- Nocturnal rise in GnRH (LH)

Mid-late puberty
- Pulsatile release GnRH throughout day

Adult
- sustained pulsatile release of GnRH, Females have cyclic changes

34
Q

According to Tanner stages, when does menarche begin?

A

Menarche doest start til Tanner stage 4 - fertility doesn’t kick in til ~1 yr later as reproductive system still getting used to new role for follicular maturation and selection

35
Q

At what tanner stage does sperm production begin?

A

Sperm production in males begins at Tanner stage 2

36
Q

What are the potential adverse risks of precocious puberty?

A
  • cardiovascular disease
  • metabolic disease
  • obesity
  • diabetes
  • disordered behaviour
  • decreased adult height
  • decreased life expectancy
37
Q

what factors control onset pf puberty?

A

Dialogue between our individual genetics and environmental factors
All impinge at different points of the HPG axis

38
Q

What are the theories of precocious puberty?

A
  • Inherent maturation of CNS
  • Body fat/nutrition: Leptin + Ghrelin?
  • Hypothalamic hormones: Kisspeptin, other factors?
  • Latest theories - Epigenetics?
39
Q

What is the effect of energy extremes on puberty?

A

Extremes of energy excess (body fat mass) impact the timing of puberty in both sexes - particularly females

40
Q

What is the effect of nutrition on puberty onset?

A

Under- and over-nutrition in foetal and/or neonates alters the timing of puberty in rodents and humans

Morbid obesity (females) can cause precocious puberty

41
Q

How do nutritional signals effect the HPG axis?

A

Secretions from the gut and adipose tissues act upon the hypothalamus which regulates gonadal function via the HPG axis

42
Q

What are the key nutritional signals involved in puberty?

A

Key secretions involved are leptin and ghrelin

43
Q

Describe the pathologies of ob/ob leptin deficient mice

A 
Hyperphagic
Hyperglycaemic
Insulin resistant
Infertile
Leptin deficient
44
Q

Where is leptin expressed?

A

Expressed in adipocytes- White Adipose Tissue
Sensor of energy sufficiency
Satiety factor - tells brain you’re full
Stimulates energy expenditure

45
Q

How do levels of leptin correlate with body fat?

A

Circulating levels directly proportional to amount of body fat
Leptin deficient
- brain doesn’t receive satiety signal so continue eating

Receptor is desensitised to leptin
- don’t receive satiety signal

46
Q

What are the effects of leptin deficiency on puberty?

A

ob/ob mice & humans - hypogonadotrophic hypogonadism

Delayed/absent puberty
Can be reversed with recombinant leptin injection

Some leptin-deficient patients have normal menses / LH / E2 levels - unknown why.

47
Q

How does leptin affect puberty onset in males and females?

A

Sexual dimorphism:

  • Females- rise ~ 2 years prior to puberty (increased GnRH pulsatility)
  • Males- no rise
48
Q

How does obesity affect levels of leptin?

A

Obesity increases leptin and earlier puberty occurs

49
Q

What are the conclusive effects of leptin so far?

A

Threshold of leptin required to be reached for puberty but not a driver of puberty itself.

Leptin has a permissive role on puberty onset, not the ‘driver’

50
Q

What is the role of ghrelin

A

Ghrelin senses the fasted state, to stimulate feeding and fat deposition.
- appetite stimulating hormone

51
Q

What is the effect of ghrelin on the hypothalamic-pituitary?

A

A bolus of ghrelin stimulates the GH/IGF axis Via Growth Hormone Secretagogue Receptor GHSR.

52
Q

How does ghrelin affect HPG axis?

A

In ‘starvation’ (high ghrelin) decreased activity of the HPG axis.

53
Q

How do ghrelin levels change in puberty?

A

Ghrelin decreases as puberty proceeds

54
Q

What are the effects of ghrelin on Kisspeptin?

A

Ghrelin can decrease hypothalamic kiss1 expression in rats (Forbes et al., 2009).

Subset of kiss1 neurons in selective hypothalamic nuclei that express GHSR and respond to Ghrelin.

55
Q

Describe the relationship of GnRH and KISS1R

A

Co-expression of GnRH mRNA with Kiss1R mRNA in rats from the medial preoptic area.

56
Q

What is the role of kisspeptin in puberty?

A

Kisspeptin directly stimulates GnRH activity
Proves activity of kisspeptin upstream of GnRH

GnRH activity reactivated in puberty and modulated by kisspeptin activity

57
Q

What disorders were present in mice with KISS1r deficiency?

A

Abnormal development of GnRH neurones 🡪 hypogonadism

Failure to enter puberty
KO mice for GPR54 or kisspeptin 🡪 hypothalamic hypogonadism

Mutations in humans:- hypothalamic hypogonadism
Activating mutations of GPR54 🡪 precocious puberty

58
Q

Phenotypically what are the characteristics associated with KiSS1r/GPR54 deficiency in males and females?

A

Male: small testes and epididymis, delayed spermatogenesis infertility;

Female: small oviducts, folliculogenesis-no progression to ovulation, no oestrous cycles, infertility

59
Q

How does nutrition affect kisspeptin release during puberty?

A

Only in pubertal mice is the level of kisspeptin expression markedly reduced; not in the adult mice during fasting state

60
Q

Outline the integration of metabolic cues and kisspeptin-GnRH system

A
  • Reduced leptin in starvation, decreased GnRH secretion
  • Leptin directly excites Kiss1 neurones in ARC
  • Leptin deficiency »↓Kiss 1 mRNA in ARC
  • But only 10-40% of Kiss1 neurones express LepR

Science of Reproduction (32 decks)

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