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Physiology 2 > HPG Axis II > Flashcards

HPG Axis II Flashcards

1
Q

What is puberty?

A

The transition from a non-reproductive to a reproductive state

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2
Q

What do the gonads produce?

A

Mature gametes
Testes produce spermatozoa
Ovaries develop oocytes you were born with

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3
Q

What kind of changes occur upon puberty to a male or female?

A

Females’ breasts develop

Males’ testicular volume increase

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4
Q

What is the difference between primary and secondary sexual characteristics?

A

Primary characteristics you are born with e.g. penis and vagina
Secondary characteristics develop in puberty e.g. physiological changes (hair, height, body shape) and psychological changes (CNS remodelling)

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5
Q

What are the 2 endocrine events of puberty?

A

Adrenarche leading to puberache
increase in adrenal androgen secretion
causes growth of pubic hair, axillary hair, height
it is the initial growth spurt

Gonadarche
awakening of HPG axis
Increased GnRH secretion increased LH/FSH secretion
Causes development of secondary sexual characteristics

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6
Q

What do both adrenarche and gonadarche result in? What means that you can have 1 without the other?

A

Complete puberty

They are independently regulated

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7
Q

What happens in adrenarche?

A

Zona reticularis of adrenal cortex secretes DHEA and DHEAS (androgens)
Due to cellular remodelling of the adrenal cortex
Gradual increase in levels from 6 to 15 years old
20 fold increase peaking at 20-25 years old
Declines thereafter

No change in other adrenal steroids
No known mechanism to trigger it

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8
Q

What causes pubarche occur?

A

Adrenarche - increase in the adrenal androgen secretion

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9
Q

What happens in pubarche?

A

Pubic and axillary hair appear
Increase in sebum production from pilosebaceous units (can lead to acne - infection or abnormal keratinization also leads to acne)

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10
Q

What is defined as precocious puberty?

A

Before 8 years old for girls or before 9 years old for boys

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11
Q

When does gonadarche occur?

A

Several years after adrenarche (around 11 years old, when the HPG axis is reactivated)

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12
Q

What is gonadarche?

A

Reactivation of the HPG axis - gradual rise of pulsatile release of GnRH
Can produce viable gametes with ability to reproduce
Via hormones

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13
Q

Why is the HPG axis ‘reactivated’ in gonadarche?

A

In the foetus it is fully functioning since it is needed for male differentiation

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14
Q

What does GnRH come from?

A

ARC (arcuate nucleus) has aggregation of GnRH neurons from which GnRH is produced

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15
Q

When is the HPG axis first activated?

A

In the 16th week of gestation (baby developing inside womb)

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16
Q

When does the HPG axis and thus GnRH secretion first get seized? Then what happens?

A

1-2 years postnatally

Then it is restrained for 10 years or more

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17
Q

Why can you tell the sex of a baby by the 20th week scan during pregnancy, but not the 12th week scan?

A

Reactivation of the HPG axis in the 16th week developed the penis/ didn’t

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18
Q

How does GnRH and therefore LH secretion change during puberty?

A

Early puberty - nocturnal rise

Early mid to mid puberty - more frequent rise in 24 hour period

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19
Q

Why is LH used experimentally over GnRH?

A

People don’t give permission to view their hypophyseal portal circulation, so LH is used since it mimics GnRH

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20
Q

What are the potential theories for causes of the onset of puberty?

A
  1. Maturation of 800-1000 GnRH synthesizing neurons inherently/ genetically occurs at time of puberty
  2. Environmental/ genetic factors e.g. epigenetic signals acting on genome and so timing of puberty
  3. Kisspeptin
  4. Body fat/ nutrition
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21
Q

What is Frisch’s hypothesis?

A

Certain % of body fat and weight required for first menstrual cycle to occur (menarche)
17% body fat

22% body fat required for reproductive ability to be sustained
Need enough body energy reserves for foetus to grow/ for baby to live an individual life upon birth

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22
Q

HPG axis dysfunction can lead to metabolic dysfunction and Polycystic Ovary Syndrome (PCOS) - what is that?

A

Elevated androgens (male hormones) in females

23
Q

What does anorexia nervosa/ intensive physical training (i.e. athletes) lead to in terms of HPG axis dysfunction? How can this be restored?

A 
Reduced response to GnRH
So lower gonadotropin levels (LH/ FSH)
So amenorrhea (lack of menstrual cycle)

Restored when nourished/ exercise is stopped

24
Q

What are leptin and ghrelin?

What do they do to kisspeptin?

A

Leptin - satiety factor
Ghrelin - appetite stimulator
They regulate kisspeptin

25
Q

What happens when there is an inactivating mutation for KISS1R (it’s receptor) or the gene coding for kisspeptin?

A

Hypogonadism - small and underdeveloped gonads
So failure to enter puberty
And hypogonadotropic hypogonadism
No GnRH, so no LH/FSH, so no +ve drive to testes/ ovaries to produce sperm/ develop the follicles

26
Q

What happens if there is an activating mutation of the KISS1R?

A

Precocious puberty

27
Q

What is consonance?

A

The smooth ordered progression of changes that occur through puberty

28
Q

What does the order of pubertal changes being uniform mean?

A

The changes follow a specific order

29
Q

How does puberty vary between people?

A

Age of onset
Length of puberty (time it takes for stages to occur + time between stages)

Large inter individual differences/ how far on people can be in puberty differs for same ages

30
Q

What are the signs of puberty beginning?

A

Breast budding in females and genital development in males

31
Q

What are the historical trends for menarche?

A

Average age is 12.5 years but this is decreasing (same with average age at which boy starts puberty)

32
Q

Describe Tanner’s stages of puberty and what it is used to determine

A

5 stages; 1 is prepubertal and 5 is at the end of puberty

3 different parameters
Breast development, pubic hair, genital development

Determines - if there is precocious puberty, puberty inconsonance, other clinical evaluations

33
Q

What are the physical changes in girls during puberty?

A

Thelarche (breast enlargement) - one of first things to happen + first sign of oestrogen activity)
Pubic/ axillary hair
Uterus enlarges + it’s cytology changes (cellular composition change due to oestrogen production in ovary)
Uterine tube, vagina and cervical changes
Height changes (earlier than boys, peak height velocity is 9cm per year at age 12)
Body shape changes - hips widen
HPG axis reactivates - increase in ovarian size as follicles develop
Menarche occurs - occurs in tanner stage 4, takes a year for female to become fertile after this

34
Q

What are menstrual cycles like in the 1st year after menarche?

A

Irregular (as HPG axis fine tunes) and anovulatory (ovulation doesn’t occur)

35
Q

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

A

Testicular volume, penis (response to testosterone), scrotum all grow
Scrotum skin changes
Vas deferens, seminal vesicles and prostate’s lumen increases - all androgen dependent events
Body/ facial/ pubic/ axillary hair grow (due to adrenal androgens in andrenarchy)
Larynx enlarges due to androgens - adams apple (projection of thyroid cartilage), voice deepens
Height increases - PHV is 10.3cm/y and is reached at 14 years old
Body shape changes - shoulders broaden

36
Q

When are males fertile?

A

From the onset of puberty

Testosterone from leydig cells stimulates meiosis and spermatogenesis in sertoli cells

37
Q

At the start of puberty, by how much does testicular volume increase by and how is this measured?

A

Beyond 4 ml in volume

Clinicians use beads - prader orchidometer

Adult should be 20-25ml

38
Q

Which hormones does the growth spurt involve?

A

Growth hormone and oestrogen (for both boys and girls) complexly interacting

39
Q

When does the growth spurt occur in boys and girls?

A

Girls have it approx. 2 years before boys and boys have it around the age of 14

40
Q

How do oestrogen levels during puberty affect bone growth?

A

Oestrogen effects epiphyseal growth (the epiphyseal plate is a hyaline cartilage plate at the end of a long bone)

The oestrogen levels go from lower to higher levels as puberty progresses

Low levels promote linear growth and bone maturation
High levels cause epiphyseal fusion
This is known as the biphasic effect of oestrogen on epiphyseal growth

41
Q

How do androgens drive the PSUs to differentiate?

A

Sebaceous PSU - androgens cause increased sebum production (can cause infection/ acne)

Vellus PSU - differentiates to form terminal PSU (forms beard hair) or APO-PSU (forms pubic/ axillary hair)
This is also androgen driven

42
Q

What are the psychological changes that occur in puberty?

A
  1. Increased need for independence
  2. Increased sexual awareness/ interest
  3. Development of sexual personality
43
Q

How does adjustment to psychological changes change with later puberty?

A

Adjustment becomes easier

44
Q

What is a disorder in which physical changes do not match psychological changes?

A

Precocious puberty

45
Q

What happens to consonance in precocious puberty?

A

Stays the same

46
Q

What happens to the HCG axis in precocious puberty?

A

Prematurely activates

Gonadotrophin-dependent precious puberty (/central precocious puberty i.e. drive from hypothalamus or pituitary):

Excess GnRH secretion (idiopathic i.e. unknown cause or secondary i.e. know cause)
Excess gonadotrophin secretion so early drive to reawaken gonads - pituitary tumour
Have consonance

Gonadotrophin-independent precocious puberty (independent activation rather than central drive via hormones):

Testotoxicosis - activating mutation of LH receptor so premature maturation of external genitalia, no changes in height and hair
Sex steroid secreting tumour (e.g. progesterone, estrodiol, androgen secreting)
Exogenous steroids
Loss of consonance

47
Q

What is an example of a gonadotrophin-independent precocious puberty syndrome?

A

McCune Albright Syndrome
G alpha S subunit activating mutation in the GNAS1 gene
Activation of adneylyl cyclase goes overdrive mimicking hormone activation of LH and FSH which work via that pathway

Other symptoms (due to the pathways of other hormones being activated) and hyperactivated adenylyl cyclase signalling) e.g. café au lait, fibrous dysplasia (normal bone and marrow is replaced with fibrous tissue, resulting in formation of bone that is weak and prone to expansion)

48
Q

What is pubertal delay?

A

Absence of secondary sexual maturation by 13 years old for girls (or absence of menarche by 18 years old) or 14 years for boys

49
Q

What happens to the HPG axis in pubertal delay?

A

It’s activation is delayed

50
Q

What are 90% of the pubertal delay cases?
Which sex are they more common to?
What are they often due to?

A

They are constitutional delay - temporary delay with no physical abnormalities causing the delay
They are 10x more common to boys
They are often the result of another chronic illness such as diabetes or cystic fibrosis

51
Q

How is pubertal delay caused by hypogonadotrophic hypogonadism?

A

A feature of hypogonadotrophic hypogonadism is there being no LH/ FSH
This means the gonads do not activate

52
Q

What happens in Kallman’s syndrome?

A

It is an example of hypogonadotrophic hypogonadism

GnRH neurons they migrate to hypothalamus from pre-optic area of the nose; triggered by developmental cues such as the KAL1 gene. An inactivating mutation in the gene (essential for GnRH neuron migration) impairs GnRH migration so GnRH is not secreted, so no LH/ FSH is produced, so the gonads do not activate

Defects in GnRH production can be in the form of a mutation in GnRH itself/ an inactivating mutation in its receptor

53
Q

How does hypergonadotrophic hypogonadism cause pubertal delay?

A

GnRH and LH and FSH production is intact but the gonads has something wrong (impaired response to the gonadotrophins)

This presents as gonadal dysgenesis (very small gonads, low volume, ovaries hard to find as they have no mature follicles). Also presents as low sex steroid levels.

This occurs to people with a normal karyotype e.g. mumps can cause it to occur.

54
Q

What are examples of gonadal dysgenesis resulting from abnormal chromosomes/ karyotypes?

A
  1. Klinefelter’s syndrome XXY or variants - female patterns of hair + breasts + longer arms + wider hips
  2. Turner’s syndrome XO - shorter than normal, underdeveloped and small ovaries (streak ovaries)

Physiology 2 (10 decks)

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