Growth Hormone Flashcards
What is the role of GHRH in GH expression?
Increases GH gene transcription
Promotes GH release
Stimulates production of GHRH receptors
Stimulates somatostatin release– Neg feedback
What is the role of somatostatin in GH expression?
Decreases pulse frequency and amplitude
No impact on GH synthesis
Inhibits GHRH release
What is the role of Ghrelin in GH expression?
Acts on growth hormone secretion receptor
Important during times of fasting/starvation
When is GH secretion the greatest?
Right after strenuous exercise and first few hours of deep sleep
ADHD medications such as Ritalin do what to children?
Interrupt deep sleep and cause stunted growth
What stimulates GH secretion?
Deep sleep Exercise Sex steroids Fasting--hypoglycemia Amino acids--arginine--decrease somatostatin release Stress a-andrenergic agonist Dopamine agonists
What inhibits GH secretion?
IGF-I Obesity Glucocorticoids Hyperglycemia Free fatty acids GH B-adrenergic agonists
How does growth hormone activate its receptors?
Binding of GH changes arrangement of receptor dimer and activates JAK2–phosphorylates/activates STAT transcription factors for GH
How is GH released from the somatotrphic cells in the anterior pituitary?
GHRH reaches the somatotroph cell in the anterior pituitary via long portal veins–stimulates Gs protein-coupled receptors–raises cAMP—activating PKA to phosphorylate the transcription factor CREB–upregulates Pit-1–increasing GH and GHRH receptors–PKA also increases Ca which leads to secretion of GH
How does somatostatin inhibit GH release from the anterior pituitary?
Somatostatin is released from the hypothalamus and goes to the anterior pituitary through long portal veins–work through Gi-protein coupled receptors inhibiting adenylyl cyclase and lowers [Ca]
What does GH stimulate in the liver and what does this effect?
IGF-1 production– stimulates hepatic glucose production
Also IGF-1 inhibits GH release
What does GH stimulate in Adipose tissue and how is this mediated?
Stimulates release and oxidation of Free fatty acids particularly during fasting
Mediated by reduction of activity of lipoprotein lipase
What does GH stimulate in skeletal muscle?
Anabolic action on skeletal muscle–stimulates amino acid uptake and incorporation into protein and cell proliferation–increases metabolism
What are high levels of GH going to cause?
blocking action of insulin–GH counteracts the affects of insulin–increases lipolysis and stimulates glucose production
What does IGF-1 induce in bone development?
clonal expansion of the early chondrocytes and maturation of later chondrocytes—leads to synthesis of extracellular matrix proteins
What 2 things are needed for the production of IGF-1?
GH and Food
What does GH do to insulin secretion and its action?
increases insulin secretion BUT blocks its action
Once IGF-1 binds its receptor what occurs?
Dimerization which leads to autophosphorylation
Autophosphoylation of the IGF-1 receptor cause what to occur?
recruits two major phosphotyrosine binding proteins–IRS-1 and Shc
After phosporylation of IRS-1 and Shc on the IGF-1 receptor what occurs?
Activation of PI3K and Ras/MAP kinase pathway–which regulate cellular transcription
What does the pubertal peak rate of growth correspond with?
serum [IGF-1]
What is Laron syndrome and what causes it? What is seen clinically with these pts? How is it treated?
Growth hormone insensitivity cause by point mutation or deletion in GH receptor
Low [IGF-1]
Normal-elevated [GH]
severe post-natal growth
Treatment– rhIGF-1
What is Acromegaly and what causes it?
Increase in GH caused by adenomas—causes protrusion of the jaw/macroglossia(large tongue)/enlarged hands and feet/carpal tunnel syndrome/reduced strength
GH deficiency causes an increase in what and decrease in what?
Increase- visceral adipose tissue/clotting factors/insulin resistance-LDL
Decrease- myocardial function
