Hypothalamic / pituitary / gonadal axis Flashcards
What do we need to reproduce?
- Correct process of sex determination + differentiation
- Sexual maturation - puberty
- Production and storage of sufficient supply of eggs + sperm
- Correct number of chromosomes in egg + sperm
- Actual sexual intercourse - egg + sperm transported + meet
- Fertilisation, implantation, embryonic + placental development
- Once delivered, to nurture individual until capabale of ‘independent’ life
In the HPG axis, what type of hormones do the hypothalamus and pituitary release?
Peptide
What type of hormones does the gonad release?
Steroidal mainly (some peptide)
What is the ‘master controller of reproduction’ hormone released by the hypothalamus? What is this hormone controlled by?
Gonadotrophin Releasing Hormone (GnRH) - controlled by kisspeptin.
Which hormones are released by the anterior pituitary?
FSH and LH
What hormones does the gonad release (male and female)?
F - Oestradiol, Progresterone
M - Testosterone
Which peptide hormones that are released from the gonad, directly regulate FSH production?
Inhibin + activin
How does GnRH reach the anterior pituitary and what result does it exert?
- Various neural inputs (kisspeptin) stimulate GnRH neurones
- GnRH released into primary plexus
- Travel to anterior pituitary
- Bind to GnRH receptors on gonadotroph cells of anterior pituitary
- FSH and LH produced + secreted into circulation
Describe the peptide structure of GnRH
Decapeptide (10 AA) -> quite tiny
Where is GnRH released from?
The GnRH neurones, located in arcuate nucleus (of hypothalamus)
What is meant by the ‘pulsatility’ within the HPG axis?
- GnRH secreted in a pulsatile fashion from hypothalamus - pulse generator orchestrated
- GnRH pulse stimulates pulse of secretion of LH and FSH from ant pit
- Pulsatile GnRH secretion = vital for stimulation of LH/FSH secretion
- Slow freq pulse favours FSH, rapid pulse freq favours LH
- Continuous release results in cessation of response
What is the difference between gonadotrophs and gonadotrophins?
- Gonadotrophs – cells in anterior pituitary that synthesise and secrete LH and FSH in response to GnRH
- Gonadotrophins – LH and FSH stimulate the ovary and testis
What is the difference between synthetic GnRH and GnRH analogues?
- Synthetic GnRH - same structure as native GnRH -> stimulatory
- GnRH analogues - modified GnRH peptide structure, loss of pulsatility -> inhibitory - they are either agonists or antagonists
What is the mechanism of action of GnRH at the GnRH receptor?
- Binding to receptor
- Activation of signalling
- Stimulation of gonadotrophin synthesis + secretion
- Dissociation of GnRH from GnRHR
- GnRHR responsive to next GnRH pulse
How is the mechanism of a GnRH agonist different to GnRH itself?
- Agonist binds to receptor in same way and does activation and stimulation of gonadotrophin synthesis + secretion too
- BUT then… uncoupling of GnRHR from G-protein
- leaves GnRHR non-responsive to GnRH
How do GnRH antagonists act at the receptor?
- Bind to receptor
- Block receptor
- No downstream effects
What are important clinical uses of GnRH analogues?
- Ovulation induction + IVF
- Prostate cancer
- Estrogen responsive breast cancer in pre-menopausal women
- Ovarian + endometrial cancers
- Gonadal protection (prior to chemo)
- Uterine fibroids
- Endometriosis
- PCOS
What is the basic structure of the gonadotrophin hormones (LH, FSH, hCG)?
- Hereodimeric peptides
- Common alpha-subunit + hormone specific beta-subunit
In gonadotrophin hormone structure, what determines biological function?
The microheterogeneity due to the N-linked carbohydrate side chains (+ O linked in hCG) - this is glycosylation which is necessary.
Which of alpha or beta subunits are synthesised in excess in gonadotrophin hormones?
Alpha are in excess
Beta-subunits limit the hormone concentration
Does biological activity depend on pulsatile secretion of gonadotrophins?
No, pulsatile secretion not necessary - eg doesn’t occur in IVF which works
What link does nutritional status have with the HPG axis in terms of gonadotrophin concentrations?
In underweight paitents, the LH and FSH levels are dramatically decreased as well as frequency being decreasd.
What is the function of LH in males?
Stimulation of Leydig cell in testes -> androgen synthesis
What is the function of LH in females?
Act at ovary:
- > theca cell androgen synthesis
- > ovulation
- > progesterone production of corpus luteum
