MEDI211 Lecture Notes - Lecture 3: Extracellular Matrix, Periosteum, Osteoblast
Week 4 Lecture 3 – Endocrine 5
Growth hormone:
•primary product of the anterior pituitary
•Single most important hormone for growth to normal adult stature —> linear growth and
body mass, so is secreted throughout life.
•Peptide hormone —> has membrane surface receptors.
•40% of it is bound to a protein in bloodstream, which enables it to last longer. This binding
protein is the extacellular domain of the GH receptor. This protein is also genetically
determined, and this is what plays a role in determining adult stature.
Biosynthesis:
•Synthesised in anterior pituitary
•DNA —> mRNA = preproGH mRNA.
•Ribosome translates mRNA into the early protein — preproGH protein.
•mRNA contains the signal sequence for translation in RER-preproGH binds to RER-signal
sequence is cleaved in the RER —> proGH.
•ProGH enters the Golgi apparatus and is processed into lots of different types of
active growth hormone.
•Hypothalamic nuclei releases the growth hormone-releasing hormone (GHRH) which travels
to the somatotropin via the portal system.
•GHRH binds to GHRH receptor on somatotroph, which activates the G-protein second
messenger system —> adenyly cyclase —> ATP to cAMP —> activates PKA —>
gene transcription —> exocytosis of active GH.
•Hypothalamic nuclei also release GHIH which has the opposite effect effect on GH release. It
inhibits the release of GH from the somatotrophs in the hypothalamus by binding to the
GPCR and inhibiting the formation of adenylyl cyclase.
Growth hormone releasing hormone effects:
1. Acute, direct, metabolic effect not related to growth:-Increases blood free fatty acid levels —
> stimulates lipolysis. This results in more energy being available in the bloodstream. -
Increases blood glucose levels —> increases hepatic glucose output whilst decreasing muscle
glucose uptake as muscles uptake FFAs instead. -Spares glucose for the brain -GH
is structurally similar to ghrelin, so binds to ghrelin receptors and stimulates appetite.
2. Long-term, indirect, growth-promoting effects:-GH does not directly cause cell
division, protein synthesis or bone growth-GH stimulates insulin-like growth factors (IGFs)
IGF-1 stimulates soft tissue, cartilage and linear bone growth during childhood and
adolescence. It also influences bone thickening in adulthood. Direct action of GH via GHr on
target cells = metabolic effectsIndirect action of GH via IGF-1 and IGF-1r on target cells =
growth-related events.
Growth hormone receptors:
•GH binds to receptors on target cels
•Receptors are tyrosine-kinase-associated receptors
•This receptor is a monomer - single protein. When GH binds to two monomers is forms a
dimer which forms a bridge.
•GH binding activates tyrosine kinase enzyme, which results in phosphorylation and a
signalling cascade in the cells.
Insulin-like growth factor:
•Mediates growth-promoting events of GH
•Synthesised mostly in liver
•Structurally similar to insulin
•IGF-1R is a tyrosine-kinase receptor
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