2. HYPOTHALAMIC-PITUITARY GONADAL AXIS Flashcards
What type of hormones are LH and FSH?
Peptide Hormones
What type of hormones are oestrogen, progesterone and androgens?
Steroid Hormones
Where are receptors for peptide hormones found?
Inside the nucleus
What does kisspeptin do?
Controls GnRH release and synthesis- makes it pulsatile
What is a GnRH analogue?
Different peptide structure to GnRH; downregulates HPG axis; can have agonist/antagonist
What does a synthetic GnRH analogue do?
Stimulates HPG axis
Where is kisspeptin produced?
Neurones in the brain- at first kisspeptin is inactive, gets cleaved and then gets activated
What do we need to reproduce?
sexual intercourse, right gamete number, right chromosome number, fertilise, implant
At what point do gonads positively feedback to the hypothalamus and anterior pituitary?
LH surge
What releases LH and FSH (gonadotrophins)?
Anterior Pituitary
What do the gonads release in females?
Oestrodiol (E2) and Progesterone (P4) (STEROID HORMONES)
What types of hormones do the male gonads release?
STEROID HORMONES: Testosterone
PEPTIDE HORMONES: activin and inhibin (negative feedback of FSH)
Where is GnRH secreted from?
GnRH hormones in the hypothalamus
Where is GnRH released into?
Hypophyseal portal circulation
What does GnRH bind to ?
Gonadotroph cells on the anterior pituitary
Which hormone can feedback negatively and positively?
Oestrogen- only during ovulation
What are the functions of the HPG axis?
gamete production in males, growth and development in males and females
Give an outline of the hypophyseal circulation
- neuronal kisspeptin neurones act on GnRH neurones
- GnRH released into primary plexus
- Go into median eminence
- Travel via hypophyseal portal vessel to ant pituitary
- GnRH bind to gonadotroph cells
- LH and FSH release
What type of hormone is kisspeptin?
Peptide hormone
Where is kisspeptin expressed?
In arcuate and AVPV nuclei in hypothalamus
What receptor does kisspeptin bind to on GnRH
GPR54 (aka kiss-1)
wHAT Is kisspeptin cleaved from?
pro-pro kisspeptin peptide structure
What is the largest kisspeptin cleaved form?
kisspeptin 54 (METASTIN)- the biggest one - can be cleaved to form smaller ones kp-14, kp-13, kp-10. KP-54 can cross BBB All have a C-terminal region that contains an Arg–Phe–NH2 motif characteristic of the RF-amide peptide family, which allows them to fully activate KISS1 receptor.
Where are GnRH neurones found?
in the parvocellular system
What is a GnRH pulse generator?
small collection of GnRH neurones- maintain pulsatility, speed and frequency of GnRH pulse generation.
What type of peptide is GnRH?
Decapeptide= 10 amino acids
What is GnRH released with?
GAP (GnRH associated protein)- (56 amino acids long) function unknown but maybe to do with prolactin release
How often is GnRH released?
pulsatile- every 30 to 120 minutes
Why is pulsatile release of GnRH important?
pulsatile GnRH release= pulsatile LH and FSH release
if GnRH not pulsatile- then no LH/FSH release bc GnRH receptor desensitizes
What does rapid GnRH pulse favour?
LH release Fast pulses are 30 to 60 mins
What does slow GnRH pulse favour?
FSH release Slow pulses are 60 to 90mins
What does synthetic GnRH do?
- GnRH binds to the GnRH receptor
- signalling in cell is activated
- stimulates gonadotrophin synthesis and secretion
- GnRH dissociates from GnRH receptor
What does GnRH analogue (agonist) do?
- bind to receptor
- signalling activated
- gonadotrophin synthesis and secretion
- few weeks - LH and FSH surge
- GnRH gets uncoupled (stays binding)
- GnRH receptor non-responsive to GnRH
- no LH/FSH released
Where are GnRH analogues used (CLINICAL USES)?
prostate cancer, IVG, ovulation induction, breast cancer, ovarian cancer, endometrial cancer
Used controversially as gonadal protection prior to chemotherapy
- > Uterine fibroids
- > Endometriosis
- > Polycystic ovary syndrome
What are the gonadotrophins?
LH, FSH, hCG= heterodimeric peptides (alpha and beta subunits)
What do all gonadotrophins have in common?
alpha subunit (glycosylated residues)
Why are the beta subunits different in gonadotrophins?
different glycosylation and diff amino acid length
Why is glycosylation important?
glycosylation needed to activate the receptor
carb side chains (glycosylation) change with pregnancy and menstrual cycle (hCG becomes hyperglycosylated)
wHAT Is the function of LH in males?
testis= stimulate leydig cells= produce testosterone
What is the function of LH in females?
theca cells= produce androgens
LH= ovulation
second half= coordinates progesterone production from corpus luteum
What is the function of FSH in males?
sertolli cells= spermatogenesis
What is the function of FSH in females?
follicle maturation
granulosa cell proliferation- produce oestrogen
androgen from theca cells transported to granulosa cells= aromatase- convert to oestrogen
What kind of gland is the pituitary gland?
endocrine
what artery delivers blood to the infundibulum?
The superior hypophyseal artery delivers blood to capillary network in upper infundibulum
What is the blood supply to the posterior lobe of the pituitary gland?
Inferior hypophyseal artery
What can you give a patient if they are anovulatory (dont ovulate)
Give timed pump giving GnRH every 90 minutes
Which subunits are made in excess in gonadotrophins?
α-subunits are synthesized in excess with β-subunit limiting the hormone concentration.
What is the difference between LH,FSH and hCG?
LH/FSH have N-linked carbohydrate side chains
hCG has N-linked and O-linked
