Growth Hormone Flashcards
what is another name for growth hormone, where is it produced and what type of hormone is it?
somatotropin
anterior pituitary
polypeptide
what is the effect of GHRH?
increases GH gene transcription and release, stimulates GHRH receptor production and stimulates somatostatin release
what is the effect of somatostatin?
decreases pulse frequency and amplitude of GH release, no impact on GH synthesis and inhibits GHRH release
what is the effect of ghrelin? what is it most important for?
stimulates hunger, acts on growth hormone secretagogue receptor
important for feeding behavior, energy regulation and sleep
describe the secretion of growth hormone
released in pulsitile manner with pulses primarily at night
how does GH secretion change during puberty? exercise?
larger pulse amplitudes but no increase in number
surge in GH with exercise
how does ritalin affect growth hormone?
it disrupts sleep and causes decrease in GH secretion
what is a clinical test to provoke GH secretion?
insulin induced hypoglycemia
how do amino acids increase GH release?
by decreasing somatostatin release
how is the half life of GH prolonged after release?
by associating with GH binding protein
what is GH secretion stimulated by?
deep sleep, exercise, sex steroids, hypoglycemia, amino acids, stress, alpha adrenergic agonists and dopamine agonists
what is GH secretion inhibited by?
IGF-1, obesity, glucocorticoids, hyperglycemia, free fatty acids, GH, and beta adrenergic agonists
what does obesity do to GH secretion?
decreases the number of pulses and the duration of each pulse
from where is GHRH released? what does it do?
the arcuate nucleus of the hypothalamus
increases cAMP and Ca> PKA activation
what are the effects of PKA activation with GHRH release?
phosphorylation of CREB transcription factor- increasaes transcription of Pit-1
increases GH and GHRH receptor
what does the increase in intracellular calcium do with GHRH activation?
leads to secretion of GH
what hypothalamic neurons synthesize somatostatin? what does it do?
the periventricular region
through Gi coupled receptor> lowers cAMP and Ca
what are the major sites of action of GH?
bone, liver and adipocyte
what do the receptors for growth hormone activate?
the JAK/STAT pathway of signal transduction causing receptor dimerization and association of JAK tyrosine kinases JAKs phosphorylate the STATS- dimerize and activate transcription
what is a target gene of the GH stimulated JAK/STAT pathway?
CISH
how does GH mediate indirect effects?
works through somatomedians like IGF-1
what is the effect of GH in the liver?
stimulates IGF-1 production and glucose production
what is the effect of GH in adipose tissue?
stimulates release and oxidation of fatty acids especially with fasting
decreased lipoprotein lipases and lipogenesis
what is the effect of GH in skeletal muscle?
stimulates amino acid uptake and protein synthesis, cell proliferation and changes muscle fiber distribution
supresses protein degredation
what effect does GH have on the brain?
affects mood and behavior
what effect does growth hormone have on bone?
supports stem cell differentiation into chondrocytes
what effect does IGF-1 have in the bone?
causes proliferation of chondrocytes and maturation. leads to synthesis of ECM and calcification
besides the liver, where is IGF-1 synthesizes?
in the kidney and skin
when does GH not induce growth?
in animals that lack insulin and in the absence of carbohydrates
what are the actions of IGF-1?
stimulates growth and provides negative feedback to the hypothalamus and pituitary to decrease GH secretion
what are IGF-1 levels used for?
to screen for growth hormone deficiency because it is reflective of GH levels and more stable.
describe the similarities and differences among IGF-1, IGF-2 and insulin.
all three share three domains (A, B and C)
C region is cleaved from insulin during processing
IGF 1 and 2 have a short D domain
IGF 2 not regulated by growth hormone
describe the similarities and differences among insulin and IGF receptors
insulin and IGF 1 receptors are heterodimers: S-S bond
cytoplasmic portin has tyrosine kinase
IGF 2 is single polypeptide chain with no kinase domain
how does IGF correlate to puberty?
peak of growth rate corresponds to peak serum levels of IGF 1- both shifted to older age in males
what are some causes of GH deficiency?
absence of pituitary stalk, TBI. cranial radiation, function of development, and mutations in GH-1 gene
what is the treatment of GH? what are the results?
give exogenous GH (doesn’t work in mutation in GH1 gene)- patient does not increase growth above what is attained with normal levels
describe laron syndrome
mutation in GH receptor, low IGF-1 concentration, normal or elevated GH, post-natal growth failure
how can laron syndrome be treated?
with administration of rhIGF-1 right before puberty
what does laron syndrome prevent?
cancer, diabetes and acne
what is the difference between gigantism and acromegaly?
gigantism- had too much GH throughout life
acromegaly- caused by GH secreting adenomas in adulthood
what are the symptoms of acromegaly?
protrusion of the jaw, macroglossia, enlarged hands and feet, carpal tunnel and reduced strength
what are the consequences of GH deficiency in adults? what is it treated with?
reduces strength and bone loss, increases interstitial fat, insulin resistance, clotting factors, CVDand increases anxiety
treat with rhGH
how is growth factor related to aging?
decreased levels in aging cause loss of muscle mass and increase in interstitial body fat
what are the benefits of replacement GH with aging? what are the side effects?
restores muscle and reduces fat
side effects: insulin resistence, diabetes, edema and carpal tunnel
what is growth hormone treatment approved for?
GH deficiency, idiopathic short stature, turner syndrome, prader-willi syndrome, chronic renal insufficiency and small for gestational age
how do nutritional deficiencies impact growth?
decrease levels of IGF-1 and slow growth
why does hypothyroidism reduce growth hormone production?
because there is a thyroid hormone response element upstream of the growth hormone transcriptional start site
what are two causes of short stature with normal hormone status?
turner syndrome and down syndrome
what is short stature in turner syndrome attributed to?
haploinsufficiency of SHOX gene (expressed on hypertrophic zone during childhood
describe growth with turner’s syndrome.
slower velocity growth during childhood and scant pubertal growth spurt
describe the stature of people with extra sex chromosomes
they are taller than normal
they don’t go into puberty and don’t fuse their bones- grow longer than normal time
