Hypothalamic-pituitary-gonadal Axis I Flashcards
What do we need to reproduce?
Correct sex determination and differentiation process
Sexual maturation
Production and storage of sufficient supply of eggs and sperm
Sexual intercourse
Fertilisation, implantation, embryonic and placental development
What are the hormones released from the hypothalamus?
All releasing hormones, gonadotropin releasing hormone (GnRH) and kisspeptin
What hormones are released from the pituitary?
Stimulating hormones, FSH, LH
What hormones are released from the gonads?
Oestradiol (E2), progesterone (P4) in females
Testosterone in females
What is the hypothalamic hypophyseal portal system?
Kisspeptin acts on the GnRH neurones to produce GnRH, which acts on the anterior pituitary to release FSH and LH into circulation
What are the neurones that produce kisspeptin?
Arcuate (ARC) nucleus and the anteroventral periventricular (AVPV) nucleus of the hypothalamus
Where does kisspeptin act?
Upstream of GnRH
How does kisspeptin start and what is it cleaved down into?
Preprokisspeptin
Kisspeptin-54 -> Kp-14, -13 or -10
What type of kisspeptin is favoured for in vivo clinical studies and why?
Kp-54
It’s the most efficient at crossing the blood-brain barrier
What type of kisspeptin is favoured for in vitro clinical studies and why?
Kp-10
Cheaper
Where is GnRH synthesised and secreted from?
GnRH neurons
What neurones control the pulsatile secretion of GnRH?
Arcuate (ARC) and medial preoptic (MPN) nucleus
What are the ARC and MPN nuclei collectively known as?
The parvocellular system
How often is GnRH secreted?
Every 30 - 120 mins
What type of pulse frequency favours FSH release?
Slow
What type of pulse frequency favours LH release?
Fast
What does continuous GnRH cause?
Cessation of response
What are the clinical uses of GnRH and their analogues?
Ovulation induction and IVF, prostate cancer, ovarian and endometrial cancers, breast cancer, endometriosis, PCOS and uterine fibroids
What type of molecule are LH and FSH?
Heterodimer peptides
What are the common and hormone specific subunits of LH and FSH?
Alpha subunits are common and beta subunits are hormone-specific
What are required for the biological function of LH and FSH?
N-linked carbohydrate side chains
Which hormone subunits are synthesised in excess and which are the limiting factor?
Alpha subunits are synthesised in excess and beta are limiting
Do LH and FSH require pulsatility to function?
No but they do need it to be released
What is the function of LH in males?
Stimulates leydig cells to synthesise androgens