Hypothalamic pituitary gonadal axis

Question 1

What do we need in order to reproduce?

Answer 1

• Correct process of sex determination and differentiation
• Sexual maturation(Puberty)
• Production and storage of sufficient supply of eggs and sperm
• Correct number of chromosomes in egg and sperm
• Actual sexual intercourse or IVF
• Need fertilisation, implantation, embryonic and placental development

Question 2

What is the HPG axis also known as?

Answer 2

Also known as the master controller of reproduction

Question 3

What is gonadal function controlled by and how?

Answer 3

Gonadal function is controlled by feedback by:

• Hypothalamic and pituitary peptide hormones
• Gonadal steroid hormones

Question 4

Hormones of HPG axis in hypothalamus

Answer 4

Gonadotropin releasing hormone(GnRH), Kisspeptin

Question 5

Hormones of HPG axis in pituitary

Answer 5

FSH and LH

Question 6

Hormones of HPG axis in Gonads

Answer 6

• Oestradiol, progesterone in females
• Testosterone in males
• Inhibin and activin

Question 7

HPG axis overflow

Answer 7

See Notes

Question 8

From the hypothalamus to pituitary

Answer 8

-GnRH is secreted into the primary plexus via the median eminence and travels down the hypophyseal portal circulation to the anterior pituitary where it acts in the gonadotroph cells to coordinate LH and FSH production

Question 9

What is Kisspeptin the controller of?

Answer 9

Master controller of puberty

Question 10

What is Kisspeptin expressed within?

Answer 10

Expressed within 2 nuclei in the hypothalamus:

-ARC and AVPV

Question 11

What is Kisspeptin upstream to and what does it regulate and why does it do this?

Answer 11

It is upstream to GnRH and regulates GnRH production. It does this because kisspeptin neurons send projections to GnRH neurons and bind to Kiss1R is expressed on GnRH neurons

Question 12

Where is GnRH synthesised and secreted from?

Answer 12

Synthesised and secreted from GnRH neurons

Question 13

In what fashion is GnRH secreted in?

Answer 13

Secreted in a pulsatile fashion - pulse generator orchetrated

Question 14

What does GnRH bind to and stimulate?

Answer 14

GnRH binds to GnRH receptor on gonadotroph cells of the anterior pituitary to stimulate the synthesis and secretion of gonadotrophin hormones(FSH and LH)

Question 15

How often is GnRH secreted?

Answer 15

GnRH is secreted in pulses from the hypothalamus every 30-120 minutes

Question 16

What does a GnRH pulse stimulate?

Answer 16

A GnRH pulse stimulates a pulse of LH and FSH secretion from the pituitary

Question 17

Why is pulsatile GnRH secretion vital?

Answer 17

Pulsatile GnRH secretion is vital for stimulation of LH/FSH secretion

Question 18

What does slow frequency pulse favour?

Answer 18

Slow frequency pulse favours FSH release

Question 19

What does rapid frequency pulse favour?

Answer 19

Rapid frequency pulse favours LH

Question 20

What does a continuous release in FSH and LH result in?

Answer 20

Continuous release results in cessation of response

Question 21

What does synthetic GnRH have the same structure as?

Answer 21

Same structure as endogenous as GnRH

Question 22

How is synthetic GnRH administered and what does it stimulate?

Answer 22

Pulsatile administration and stimulates HPG axis and fertility

Question 23

What is GnRH analogues?

Answer 23

Modified GnRH peptide structure

Question 24

How are GnRH analogues administered and what does it cause the loss of?

Answer 24

Single bolus administration and causes loss of pulsability

Question 25

What are GnRH analogues used for?

Answer 25

Used for the inhibition of HPG axis

Question 26

What can GnRH analogues be?

Answer 26

Can be agonists or antagonists

Question 27

Mechanism of GnRH analogues (agonist)

Answer 27

Agonist –> Binds to GnRH receptor –> Activation of signalling –> Stimulation of gonadotrophin synthesis and secretion –> Uncoupling of GnRH receptor from G protein signalling –> GnRH receptor is non-responsive to GnRH

Question 28

Mechanism of GnRH analogues (Antagonist)

Answer 28

Antagonist –> Binds to GnRH receptor –> Blockage of receptor –> No downstream effects

Question 29

What are the therapeutic uses of GnRH analogues

Answer 29

• Ovulation
• Induction
• Prostate cancer

Question 30

Examples of Gonadotrophin hormones

Answer 30

LH FSH and hCG

Question 31

What are gonadotrophin hormones?

Answer 31

Are heterodimeric peptides with a common alpha subunit and hormone specific beta subunit

Question 32

What do the gonadotropic hormones have and why are they required?

Answer 32

Have N-linked carbohydrate sides which are required for biological function

Question 33

What action do the free subunits have in gonadotropic hormones?

Answer 33

The free subunits have no biological function

Question 34

How are alpha and beta subunits synthesised of gonadotropic hormones?

Answer 34

The alpha subunits are synthesised in excess with beta subunits limiting the hormone concentration

Question 35

Why is there a pulsatile secretion of gonadotropic hormones?

Answer 35

Pulsatile secretion of gonadotropic hormones is due to pulsatile release of GnRH from hypothalamus. It’s not necessary for their biological function

Question 36

Function of LH in testis

Answer 36

To stimulate Leydig cell androgen synthesis

Question 37

Function of LH in ovaries

Answer 37

• To stimulate theca cell androgen synthesis
• Ovulation
• Progesterone production from corpus luteum

Question 38

FSH in testis

Answer 38

-Regulation of Sertoli cell metabolism

Question 39

FSH in ovaries

Answer 39

• Follicular maturation

- Granulosa cell estrogen synthesis

Question 40

What converts androgens to oestrogens?

Answer 40

An aromatase enzyme

Question 41

What do the actions of FSH and FSH receptor regulate?

Answer 41

Actions of FSH and FSH receptor regulate transcription and translation of aromatase