3.4 Growth Hormone (GH) Flashcards
What hormone is released by somatotropic cells?
Growth hormone (AKA somatotropin…OOOH now that all makes sense)
What hormone released by the hypothalamus STIMULATES GH secretion from somatotropic cells?
Growth Hormone Releasing Hormone (GHRH)…duh
What hormone released by the hypothalamus INHIBITS GH secretion from somatotropic cells?
Somatostatin (AKA Growth Hormone Inhibiting Hormone…GHIH)
What kind of receptor does somatostatin bind to?
Gi-coupled receptor…decreases cAMP
Besides somatostatin, what other hormone inhibits GH secretion? What kind of hormone is this (just a review question)?
Dopamine inhibits GH secretion
Dopamine is an AMINE hormone
What kind of receptor does GHRH bind to to induce GH secretion?
GPCR…makes sense since somatostatin binds to a Gi receptor
What is used to determine tissue levels of GH receptor? Why?
GH Binding Protein (GHBP)…it is the ectodomain of the GH receptor
What roles does GHBP play?
Reservoir of GH in plasma
Modulator/inhibitor of GH signaling
What kind of receptor does GH bind to to illicit growth/increased blood glucose?
Cytokine receptor –> JAK/STAT secondary messenger signal transduction pathway
What causes proportional dwarfism?
Severe GH deficiency in children
What is Laron syndrome?
Laron syndrome is an autosomal recessive GH receptor variant with insensitivity to GH
Besides DH deficiency or Laron syndrome, what else can cause dwarfism?
Turner’s syndrome
SHOX mutations/chromosomal loss
Poor nutrition
Stress
What is Turner’s syndrome?
Turner’s syndrome is loss of genes on X chromosome related to stature
Where is the homeobox gene located that can be mutated causing short stature?
Homeobox gene is located on X and Y chromosomes
What causes disproportional dwarfism?
Mutations not associated with primary dysfunction of GH endocrine axis
What are the symptoms of GH deficiency in adults?
Generalized obesity
Reduced muscle mass
Asthenia (reduced energy, weakness)
Reduced cardiac output
When is the peak secretion of GH in a typical day?
2 hours post onset of deep sleep
How can GH activity be tested?
NOT a serum sample
Do an Insulin Tolerance Test or a GHRH-arginine costimulation test
How does an Insulin Tolerance Test work?
Give insulin –> causes hypoglycemia –> secretion of cortisol (adrenals) and GH (pituitary)
What is the most common pituitary hormone deficiency? What is the typical presenting concern?
GH deficiency is the most common pituitary hormone deficiency (1/4000)
Presents with hypoglycemia (unopposed action of insulin)
How is the dose of GH determined?
Give enough GH to maintain IGF-1 levels in the mid-normal range for age/gender-matched controls
How is GH made?
Recombinant human GH (rhGH)
How is appropriate rhGH levels monitored?
Kids: growth
Adults: lipid profile, fasting glucose, bone density
What are some potential side effects of rhGH?
Antibodies…usually of little consequence
Scoliosis during rapid growth
Diabetogenic
Cortisol or hypothyroidism may inhibit growth following GH therapy
Besides GH deficiency, when else has the FDA approved rhGH use?
Muscle-wasting syndrome seen with AIDS and other diseases
In Laron syndrome, there is a GH receptor deficiency…so giving rhGH does not make any sense. What is the treatment of Laron syndrome?
rhIGF (Mecasermin or Mecasermin rinfabate)
What is the effect of IGF-1?
IGF-1 is more potent than GH at stimulating chondrogenesis at epiphyseal growth plates in children
What does mecasermin rinfabate have that mecasermin does not have?
Mecasermin rinfabate has rh-insulin-like growth factor binding protein 3 (rhIGFBP3)
Which recombinant hormone has more side effects rhIGF or rhGH? Why?
rhGH has more side effects because it is more effective in inducing growth
What are the side effects of rhIGF?
rhIGF causes hypoglycemia (take before or after a meal) and affects the liver (induces cyp450)
Who should NOT be given rhIGF?
Children with cancer and patients with closed epiphyses should NOT be given rhIGF
Hypersecretion of GH can cause gigantism/acromegaly, what usually causes hypersecretion of GH?
Pituitary adenoma of the somatotropes
Is excess growth hormone common?
No…3 cases per million
What kind of drugs can be used to treat hypersecretion of growth hormone?
Somatostatin (SSTR1-5) or dopamine (D2) analogs
GH receptor antagonist (newer)
What is an example of a dopamine agonist used to treat gigantism/acromegaly? What somatostatin agonist?
Bromocriptine (dopamine agonist)
Octreotide (long-acting somatostatin analog)
What is the name of the growth hormone receptor antagonist?
Pegvisomant
What are the effects of pegvisomant? what are the side effects of pegvisomant?
Block GH receptor (prevents dimerization) –> prevention of IGF-1 release
(Reduced IGF-1 –> increased GH via negative feedback)
Pegvisomant can cause antibody formation or liver toxicity
What needs to be considered when children are treated with cortisol?
Glucocorticoids antagonize growth promoting effects
What effect does GH have on protein, mineral, carbohydrate, and fat metabolism?
Protein metabolism is increased
Mineral metabolism is increased (greater bone density)
Carbohydrate metabolism is decreased (diabetogenic)
Fat metabolism is increased (energy)
