GnRH Flashcards
What is GnRH known as?
Master controller of reproduction
How many isoforms of GnRH exist?
23 isoforms in vertebrates – it’s highly conserved
What GnRH are found in vertebrates?
Most vertebrates have GnRH I (Classic GnRH) and GnRH II
What are the roles of GnRH?
o Neuroendocrine - HPG o Paracrine (placenta/gonads) o Autocrine (prostate/breast cancer – GnRH receptors in the cancer tissue) o Neurotransmitter (Regions of the brain)
What is the structure of GnRH?
- Synthesised as a pre-pro hormone
- Cleavage steps-= Mature GnRH and GAP
- GAP peptide- co-secreted with GnRH, unknown function
What is the migratory path of GnRH neurones?
During the embryonic period: originate outside CNS, in medial olfactory placode
Then cells migrate:
Nasal region -> brain -> medio-basal hypothalamus (forebrain)
o Numerous genes involved
What is the placode?
area of thickening of the embryonic epithelial later from which the organ/structure later develops.
What happens when the migrations goes wrong?
leads to hypogonadotropic hypogonadism – Less/no GnRH released due to lack of GnRH neurones
What is Kallmann syndrome?
• Mutation in KAL-1 gene
• Premature termination of migration
o Patients present with anosmia & hypogonadotropic hypogonadism
Where are GnRH neurones found?
GnRH neurones are expressed in the parvocellular system – includes medial preoptic nucleus and arcuate nucleus
How is GnRH released?
- GnRH is processed and packaged into storage granules that are transported down the axons to the external zone of the median eminence. GnRH released in synchronized pulses from the GnRH nerve endings into hypophyseal portal system.
- Released in Rhythmic pulses - every 30-120 minutes – “circhoral pulses”
What is the GnRH pulse generator?
collection of hypothalamic neurons producing endogenous secretory rhythms
What is GnRH’s half life?
2-4 minutes
What does GnRH do?
- GnRH stimulates synthesis and secretion of gonadotrophins.
* Differential frequency and amplitude alter pattern of FSH and LH secretion, therefore impact gonadal response
What is the structure of the GnRH receptor?
- G-protein-coupled receptor (GPCR)
- 7-transmembrane domain structure, but unlike other members of GPCR does not have a carboxyl-terminal tail – for evolutionary purpose in humans, plays a role in making it resistant to desensitisation
o In desensitisation: c terminal tail is phosphorylated, receptor is internalised
How many variants of the GnRHR exist?
• Two variants Type I and II GnRHR:
o Type 1- full length, classical receptors, in humans
o Type 2 - missense truncation, mRNA is expressed but the protein and receptor is not translated and expressed