GnRH

Question 1

What is GnRH?

Answer 1

GnRH stimulates the synthesis and secretion of gonadotrophin

• Gene on chromosome 8
• 23 isoforms in vertebrates
• Most vertebrates – GnRH I & GnRH II

Question 2

What is the structure of GnRH

Answer 2

• Initially synthesised as pre-pro hormone
• Proteolytic cleavage  mature GnRH & GnRH-associated peptide (GAP)
• GnRH = 10aa sequence
• GAP co-secreted with GnRH, unknown function
• Parvocellular system (medial preoptic nucleus & arcuate nucleus) produce GnRH

Question 3

Describe the migratory path for GnRH neurones

Answer 3

GnRH neurones originate in the medial olfactory placode but it migrates to the hypothalamus during the embryological period.

During this migration, the neurones are responsive to a lot of genetic cues that regulate this migratory process.

The kal 1 gene is important for migration and mutation in the gene leads to a failure in migration resulting in kallman’s syndrome.

Question 4

Describe Kallman syndrome

Answer 4

o Mutation in KAL-1 gene
o Premature termination of migration
o Anosmia (loss of smell) & HH

Anosmia = due to GnRH neurones still being in the olfactory region

Question 5

Explain GnRH release

Answer 5

• GnRH processed & packaged into storage granules that are transported down the axons to the external zone of median eminence
• GnRH released in synchronised pulses from the GnRH nerve endings into hypophyseal portal system
• Rhythmic pulses – every 30-120mins
• GnRH pulse generator – collection of hypothalamic neurons producing endogenous secretory rhythms
o Sub-population of kisspeptin neurones in the arcuate nucleus
• GnRH t1/2 2-4 mins – degraded quickly in system
• GnRH stimulates synthesis and secretion of gonadotrophin
• Differential frequency & amplitude alter pattern of FSH & LH secretion = impact gonadal response