Hypothalamic pituitary gonadal axis Flashcards
What do we need in order to reproduce?
- 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
What is the HPG axis also known as?
Also known as the master controller of reproduction
What is gonadal function controlled by and how?
Gonadal function is controlled by feedback by:
- Hypothalamic and pituitary peptide hormones
- Gonadal steroid hormones
Hormones of HPG axis in hypothalamus
Gonadotropin releasing hormone(GnRH), Kisspeptin
Hormones of HPG axis in pituitary
FSH and LH
Hormones of HPG axis in Gonads
- Oestradiol, progesterone in females
- Testosterone in males
- Inhibin and activin
HPG axis overflow
See Notes
From the hypothalamus to pituitary
-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
What is Kisspeptin the controller of?
Master controller of puberty
What is Kisspeptin expressed within?
Expressed within 2 nuclei in the hypothalamus:
-ARC and AVPV
What is Kisspeptin upstream to and what does it regulate and why does it do this?
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
Where is GnRH synthesised and secreted from?
Synthesised and secreted from GnRH neurons
In what fashion is GnRH secreted in?
Secreted in a pulsatile fashion - pulse generator orchetrated
What does GnRH bind to and stimulate?
GnRH binds to GnRH receptor on gonadotroph cells of the anterior pituitary to stimulate the synthesis and secretion of gonadotrophin hormones(FSH and LH)
How often is GnRH secreted?
GnRH is secreted in pulses from the hypothalamus every 30-120 minutes
What does a GnRH pulse stimulate?
A GnRH pulse stimulates a pulse of LH and FSH secretion from the pituitary
Why is pulsatile GnRH secretion vital?
Pulsatile GnRH secretion is vital for stimulation of LH/FSH secretion
What does slow frequency pulse favour?
Slow frequency pulse favours FSH release
What does rapid frequency pulse favour?
Rapid frequency pulse favours LH
What does a continuous release in FSH and LH result in?
Continuous release results in cessation of response
What does synthetic GnRH have the same structure as?
Same structure as endogenous as GnRH
How is synthetic GnRH administered and what does it stimulate?
Pulsatile administration and stimulates HPG axis and fertility
What is GnRH analogues?
Modified GnRH peptide structure
How are GnRH analogues administered and what does it cause the loss of?
Single bolus administration and causes loss of pulsability
What are GnRH analogues used for?
Used for the inhibition of HPG axis
What can GnRH analogues be?
Can be agonists or antagonists
Mechanism of GnRH analogues (agonist)
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
Mechanism of GnRH analogues (Antagonist)
Antagonist –> Binds to GnRH receptor –> Blockage of receptor –> No downstream effects
What are the therapeutic uses of GnRH analogues
- Ovulation
- Induction
- Prostate cancer
Examples of Gonadotrophin hormones
LH FSH and hCG
What are gonadotrophin hormones?
Are heterodimeric peptides with a common alpha subunit and hormone specific beta subunit
What do the gonadotropic hormones have and why are they required?
Have N-linked carbohydrate sides which are required for biological function
What action do the free subunits have in gonadotropic hormones?
The free subunits have no biological function
How are alpha and beta subunits synthesised of gonadotropic hormones?
The alpha subunits are synthesised in excess with beta subunits limiting the hormone concentration
Why is there a pulsatile secretion of gonadotropic hormones?
Pulsatile secretion of gonadotropic hormones is due to pulsatile release of GnRH from hypothalamus. It’s not necessary for their biological function
Function of LH in testis
To stimulate Leydig cell androgen synthesis
Function of LH in ovaries
- To stimulate theca cell androgen synthesis
- Ovulation
- Progesterone production from corpus luteum
FSH in testis
-Regulation of Sertoli cell metabolism
FSH in ovaries
- Follicular maturation
- Granulosa cell estrogen synthesis
What converts androgens to oestrogens?
An aromatase enzyme
What do the actions of FSH and FSH receptor regulate?
Actions of FSH and FSH receptor regulate transcription and translation of aromatase
