Growth Hormone Flashcards
Explain the GH-IGF axis/hypothalamus-pituitary-liver-axis.
Hypothalamus releases GnRH (+) and SS (-) to pituitary. Ghrelin (+). GH. GHbinding protein. GH binds to liver, signal transduction, IGF synthesis. IGF circulates. Target cell - IGH binds - signal transduction and growth. Negative feedback on pituitary.
GH?
Growth hormone.
Single chain polypeptide.
Max secretion at night.
Effects are indirect.
GHBP?
Growth hormone binding hormone - increase half life to 1 hour.
GH receptor?
Signalling pathway = similar to leptin. JAK2/STAT signaling cascase.
Increase number of receptors are birth and plateau in adulthood.
GH receptor deletion.
Sever postnatal growth retardation
Proportionate dwarfism and delayed puberty.
Still some growth due to insulin?
IGF?
Bound to proteins increase half life from 10 minutes to 3 hours.
IGF receptor
Transmembrane tyrosine kinase. Similar to insulin receptor. Signal transduction... MAPK couples to mitogenesis Protein kinase B pathway results in cell survival = growth.
Effects of IGF at target tissue?
Increase protein synthesis.
Increase growth of organs.
Cartilage formation and bone growth.
Decrease GH secretion?
Hypothalamic failure - insufficent GHRH secretion
GHRH receptor mutations - decrease GH and IGF - therefore inject GH
AP failure - german sheperd dog dwarfism - inject GH.
Defects in GH receptor
Mutated - resistant to GH - Laron Syndrome.
High GH low IGF - IGF injections.
Defects in IGF-1 secretion?
IGF-1 gene deletion - growth retardation, high GH, no -ve feeback -IGF injections.
Defects in IGF receptor
Embryonically lethal.
Gigantism?
Oversecretion of GH PRE puberty.
Pituitary adenoma
Excessive height with proportionate growth.
Treatment; remove tumor, SS analogues.
Acromegaly?
Oversecretion of GH POST puberty - pititary adenoma.
Epiphyseal growth plates have closed - thickening of bones (jaws, fingers and toes).
Remove tumor, SS analogues.
Effects of GH?
Increase lipolysis.
Decrease gluconeogenesis and decrease glucose uptake.
