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
What is the function of LH in females?
Theca cell androgen synthesis
ovulation
progesterone production in the corpus luteum
What is the function of FSH in males?
Regulation of the Sertoli cell metabolism
What is the function of FSH in females?
Follicular maturation and granulosa cell oestrogen synthesis
Where are leydig cells found and what do they do?
In the interstitial cells between the seminiferous tubules
Produce testosterone
Where are Sertoli cells found and what do they do?
In the seminiferous tubules
Spermatogenesis
Where are theca cells found and what do they do?
In the lining of the antral follicle
Produce androgens
Where are granulosa cells found and what do they do?
Immediately surrounding the oocyte
Produce oestrogen
Where is the corpus luteum found and what does it do?
Has both LHR and FSHR to produce progesterone and oestrogen in the Luteal phase
What does +ve feedback of oestrogens trigger?
Ovulation
What are some examples of oestrogens?
Oestradiol and oestrone
When are oestrogens secreted?
Folliculogenesis
What are androgens important in?
Spermatogenesis
What are some examples of androgens?
Androstenedione
Testosterone
Dihydrotestosterone
What does progesterone do?
Prepares the uterus for egg implantation and maintains conditions needed for the early stages of pregnancy
