Howell-Growth Hormone Flashcards
GH is also known as ______
What type of hormone is it?
Where is it synthesized?
Growth Hormone (GH) is also called somatotropin
GH is a polypeptide hormone
Synthesized in anterior pituitary
GH in excess in childhood is called______
GH in excess in adulthood is called _______
GH deficiency during childhood________
GH deficiency during adult can lead to _______ (condition)
gigantism
acromegaly
dwarfism
GH deficiency in adult can lead to heart disease
GH receptors activate the _________ pathway of signal transduction.
How does this signal transduction generally work?
JAK/STAT
The binding of GH to their receptors cause a conformational change to a crossover conformation which repositions JAK2 tyrosine kinases leading to activation of JAK kinases by autophosphorylation, dimerization of STATs, translocation of dimerized STATs to nucleus to act as transcription factors
What effect does growth hormone releasing hormone (GHRH) have on GH? How is GHRH released?
GHRH is released in a pulsatile manner Increases GH gene transcription Promotes GH release Stimulates production of GHRH receptor Stimulates somatostatin release
What effect does somatostatin have on GH?
Somatostatin decreases pulse frequency
Decrease pulse amplitude
No impact on GH synthesis
Inhibits GHRH release
How is GH released?
Pulsatile fashion
Does somatostatin increase/decrease GH synthesis?
No effect on GH synthesis, but does inhibit GHRH release and therefore decreases GH gene transcription and release
What hormone stimulates hunger and GH production during fasting?
Ghrelin
Target for design of anti-obesity drugs
The pulsatile secretion of GH.
What time of day?
Amplitude vs. frequency
Effect of exercise?
Pulses of GH are primarily at night
The # of pulses remains relatively constant however amplitude changes (larger during puberty)
Strenuous exercise causes surge in GH
What effect does obesity have on GH secretion?
Obesity decreases the number of GH pulses and duration of each pulse
What effect does fasting have on GH secretion?
Fasting increases number of GH pulses and amplitude of each pulse
What effect do the following have on GH secretion?
- glucocorticoids
- hyperglycemia
- GH circulating
- Exercise
- Deep Sleep
- Sex steroids
- Stress
- alpha adrenergic agonist
- beta adrenergic agonist
- Glucocorticoids decrease
- Hyperglycemia decrease
- GH decrease (feedback inhibition)
- Exercise increases
- Deep sleep increases
- Sex steroids increases
- Stress increases
- Alpha increases
- Beta decreases
What affect does amino acids have on GH release?
How do they accomplish this?
Amino acids increase GH release by decreasing somatostatin release
Describe the steps in GH regulation:
- Hypothalamus releases ________, that reaches somatotrophs in the _______ pituitary via the _____.
- ______ stimulates GPCRs on somatotrophs to release GH stored in secretory vesicles by increasing _____ and ______.
- The increase in ______ levels activates _____ to physphorylate the transcription factor _____.
- Ultimately the TFs upregulate _____ and _____ .
- Hypothalamus releases GHRH, that reaches somatotrophs in the anterior pituitary via the long portal veins
- GHRH stimulates GPCRs on somatotrophs to release GH stored in secretory vesicles by increasing cAMP and Ca2+
- The increase in cAMP levels activates PKA to physphorylate the transcription factor CREB
- Ultimately the TFs upregulate GH and GHRH-Receptor.
Describe the steps in GH regulation:
- Somatostatin synthensized in the ______travels to the _____pituitary via the _______.
- Somatostatin acts by inhibiting _______ and therefore lowers ______ levels, which ultimately decreases the secretion of GH
- Somatostatin synthensized in the PVN of hypothalamus travels to the anterior pituitary via the long portal veins
- Somatostatin acts by inhibiting adenyl cyclase and therefore lowers Ca2+ levels, which ultimately decreases the secretion of GH
What effect does GH have on glucose uptake and lipolysis?
GH decreases glucose uptake (counteracts action of insulin) and increases lipolysis.
GH decreases skeletal muscle glucose utilization, increasing lipolysis and stimulated hepatic glucose metabolism
What effect does GH have on bone formation?
GH acts directly on mesenchymal stem cells to induce differentiation into chondrocytes, and stimulates chondrocytes to produce IGF-1, which acts in autocrine manner to induce clonal expansion of chondrocyte.
GH stimulates both osteoclasts and osteoblasts
What is the screening test used for determining GH deficiency?
IGF-1 is used since its levels in the circulation are more stable and reflective of GH levels in normal individuals
A defect in which structure can affect the release of GH?
any defect affecting hypothalamo-pituitary function, such as blockage of the pituitary stalk
Can GH deficiencies be treated with recombinant GH? Why or why not?
Mutations in GH-1 gene cannot be treated with rhGH because the individual will eventually make antibodies towards it.
Will giving extra GH will increase the growth rate is normal populations?
Giving extra hormone in excess of what are normal levels does NOT increase the rate of growth above what is attained with normal levels
Point mutation or deletion in GH receptor has what effect on levels of IGF-1 and GH
What is it called?
Laron Syndrome
Markedly low IGF-I concentration
Normal or elevated GH concentration
What effect does IGF-I have on GH
IGF-I negative inhibition to anterior pituitary release of GH (downregulates GH)
Since GH acts as an anti-insulin hormone, those with increased levels of GH are at risk for what?
Type II Diabetes
How do you treat adult GH deficiency?
recombinant GH
GH is approved for use in what 7 conditions?
- GH deficiency
- Idiopathic short stature (ISS)
- Turner Syndrome
- Down Syndrome
- Prader-Willi Syndrome (PWS)
- Chronic renal insufficiency
- Small gestational age
A 4-year-old boy was diagnosed with visual disturbances due to a pituitary tumor secreting excess growth hormone. Which of the following conditions would this boy most likely develop without treatmeant?
Excess growth hormone produces gigantism in prepubertal children because the epiphyseal growth plates in long bones have not closed. The effects of growth hormone on linear growth are mediated via IGF-1.
