Physiology of Growth Hormone
Type 2 IGF Receptor
IGF receptor that binds IGF2 with high affinity and binds IGF1 with low affinity, it is the clearance receptor for IGF2
Type 1 IGF receptor
IGF receptor that has an active second messenger signaling, TYR kinase phosphorylation, has multiple pathways (SH2 pathway, PI3K/PIP2 pathway)
Type 1 IGF Receptor
IGF receptor that is a heterotetramer, binds IGF1 and IGF2 with high affinity, structurally almost identical to insulin receptor, present in almost all tissue
Type 2 IGF receptor
IGF receptor that is mostly inactive with no downstream signaling and is therefore presumed to be a clearance receptor
IGFBP-3
IGFBP that is a major carrier in circulation and stimulates endocrine function
IGFBP-4
IGFBP whose endocrine function inhibits IGF action causing serum concentrations to be low
IGFBP-6
IGFBP whose endocrine function is to bind IGF2 and inhibits its action
IGFBP-5
IGFBP whose paracrine function is as a growth factor in bone matrix
IGFBP-4
IGFBP whose paracrine function is as a growth factor in tissue specific expression, locally regulates IGF
IGFBP-2 and 6
IGFBP whose paracrine function is as growth factors in CSF
IGFBP-3
IGFBP whose paracrine function is as growth factors in follicular fluid
IGFBP-1
IGFBP whose paracrine function is growth factors in amniotic fluid
1. Hyperglcemia 2. Elevated levels of insulin 3. Elevated levels of free fatty acids
What are factors that inhibit growth hormone secretion?
1. hypoglycemia 2. High levels of amino acids (especially during starvation) 3. Stress
What are factors that stimulate GH secretion
1. Growth hormone releasing hormone (GHRH) 2. Somatostatin (SRIF)
What are the two hormones that regulate growth hormone secretion?
strenuous exercise and fasting
When does episodic release of growth hormone occur?
long loop feedback
Which feedback loop does the IGF use?
short loop feedback
Which feedback loop does the growth hormone use?
growth hormone
binds with the GH receptor on hepatocytes to stimulate the secretion of the insulin like growth factors
growth hormone
binds with the membrane bound GH receptor on muscle and adipose to stimulate growth
gigantism
caused by excessive and unregulated growth during childhood, usually by pre-closure of epiphyses in the pituitary
IGFBP proteases
cleave IGFBP into active forms
IGF Binding Proteins (IGFBP)
dynamic proteins that transport the IGFs and also exhibit some endocrine effects
acromegaly
excessive secretion of growth hormone during adulthood, usually by post-closure of epiphyses
IGFBP
extends IGF half-life and regulate availability of IGF
growth hormone binding protein (GHBP)
extends the half-life of the serum growth hormone
pituitary dwarfism
growth hormone deficiency during childhood, cause by pre-closure of epiphyses. This condition is treatable
somatostatin
hormone that inhibits the release of the growth hormone
growth hormone
in the adipose tissue stimulates lipolysis and inhibits glucose uptake
IGF
in the chrondrocytes it stimulates amino acid uptake, protein synthesis, RNA synthesis, DNA synthesis, collagen production, chrondroitin sulfate, hyperplasia, hypertrophy
growth hormone
in the liver stimulates protein synthesis, gluconeogenesis, glycogenolysis, and IGFS. It inhibits Glycogenesis
IGF
in the muscle stimulates protein synthesis, amino acid uptake, and glucose uptake
growth hormone
in the muscle stimulates protein synthesis, amino acid uptake, glycogenolyis. It inhibits glucose uptake
growth hormone
increases lipolysis in adipose tissue, reduces glucose uptake in muscles, and increases hepatic gluconeogenesis
IGF2 (Somatomedin A)
insulin growth factor important for fetal/placental growth and development. Highest concentration of circulating IGF in adults, primarily cleared from circulation by binding with IGF Type 2 receptor
IGF1 (Somatomedin C)
insulin growth factor that is primary functional hormone after birth, change in it parallel changes in growth hormone from birth to death. Lethal if knockout in transgenic mice
IGF-1
insulin growth factor that is produced in the brain, muscle and bone
growth hormone
stimulates the JAK and the STAT or MAPK pathways
Growth hormone
stimulates the liver to secrete IGF
Growth hormone
191 amino acid polypeptide with 2 disulfide bonds
IGF
mediates the effects of Growth Hormone
growth hormone binding protein
produced by metalloproteolytic cleavage (especially in adipose tissue) of the GH receptor extracellular domain
GHBP
protects growth hormone from degradation
Insulin receptor
receptor that binds IGF1 at lower affinity than insulin
Hybrid IGF-Insulin Receptors
receptors that have been proposed as a potential source and/or as a contributing factor for receptor-mediated insulin resistance
growth hormone
regulates growth, works in concert with insulin life growth factors (IGFs) to maintain and stimulate growth
growth hormone
released before eating to stimulate cellular metabolism, works in concert with IGFS and insulin to utilize glucose
IGF (1 and 2)
released from the liver to regulate maintenance and growth of tissues throughout the body
...
the secretion of growth hormone peaks during puberty and then slowly declines during adulthood
