3.4 Growth Hormone (GH)

Question 1

What hormone is released by somatotropic cells?

Answer 1

Growth hormone (AKA somatotropin…OOOH now that all makes sense)

Question 2

What hormone released by the hypothalamus STIMULATES GH secretion from somatotropic cells?

Answer 2

Growth Hormone Releasing Hormone (GHRH)…duh

Question 3

What hormone released by the hypothalamus INHIBITS GH secretion from somatotropic cells?

Answer 3

Somatostatin (AKA Growth Hormone Inhibiting Hormone…GHIH)

Question 4

What kind of receptor does somatostatin bind to?

Answer 4

Gi-coupled receptor…decreases cAMP

Question 5

Besides somatostatin, what other hormone inhibits GH secretion? What kind of hormone is this (just a review question)?

Answer 5

Dopamine inhibits GH secretion

Dopamine is an AMINE hormone

Question 6

What kind of receptor does GHRH bind to to induce GH secretion?

Answer 6

GPCR…makes sense since somatostatin binds to a Gi receptor

Question 7

What is used to determine tissue levels of GH receptor? Why?

Answer 7

GH Binding Protein (GHBP)…it is the ectodomain of the GH receptor

Question 8

What roles does GHBP play?

Answer 8

Reservoir of GH in plasma

Modulator/inhibitor of GH signaling

Question 9

What kind of receptor does GH bind to to illicit growth/increased blood glucose?

Answer 9

Cytokine receptor –> JAK/STAT secondary messenger signal transduction pathway

Question 10

What causes proportional dwarfism?

Answer 10

Severe GH deficiency in children

Question 11

What is Laron syndrome?

Answer 11

Laron syndrome is an autosomal recessive GH receptor variant with insensitivity to GH

Question 12

Besides DH deficiency or Laron syndrome, what else can cause dwarfism?

Answer 12

Turner’s syndrome
SHOX mutations/chromosomal loss
Poor nutrition
Stress

Question 13

What is Turner’s syndrome?

Answer 13

Turner’s syndrome is loss of genes on X chromosome related to stature

Question 14

Where is the homeobox gene located that can be mutated causing short stature?

Answer 14

Homeobox gene is located on X and Y chromosomes

Question 15

What causes disproportional dwarfism?

Answer 15

Mutations not associated with primary dysfunction of GH endocrine axis

Question 16

What are the symptoms of GH deficiency in adults?

Answer 16

Generalized obesity
Reduced muscle mass
Asthenia (reduced energy, weakness)
Reduced cardiac output

Question 17

When is the peak secretion of GH in a typical day?

Answer 17

2 hours post onset of deep sleep

Question 18

How can GH activity be tested?

Answer 18

NOT a serum sample

Do an Insulin Tolerance Test or a GHRH-arginine costimulation test

Question 19

How does an Insulin Tolerance Test work?

Answer 19

Give insulin –> causes hypoglycemia –> secretion of cortisol (adrenals) and GH (pituitary)

Question 20

What is the most common pituitary hormone deficiency? What is the typical presenting concern?

Answer 20

GH deficiency is the most common pituitary hormone deficiency (1/4000)

Presents with hypoglycemia (unopposed action of insulin)

Question 21

How is the dose of GH determined?

Answer 21

Give enough GH to maintain IGF-1 levels in the mid-normal range for age/gender-matched controls

Question 22

How is GH made?

Answer 22

Recombinant human GH (rhGH)

Question 23

How is appropriate rhGH levels monitored?

Answer 23

Kids: growth
Adults: lipid profile, fasting glucose, bone density

Question 24

What are some potential side effects of rhGH?

Answer 24

Antibodies…usually of little consequence
Scoliosis during rapid growth
Diabetogenic
Cortisol or hypothyroidism may inhibit growth following GH therapy

Question 25

Besides GH deficiency, when else has the FDA approved rhGH use?

Answer 25

Muscle-wasting syndrome seen with AIDS and other diseases

Question 26

In Laron syndrome, there is a GH receptor deficiency...so giving rhGH does not make any sense. What is the treatment of Laron syndrome?

Answer 26

rhIGF (Mecasermin or Mecasermin rinfabate)

Question 27

What is the effect of IGF-1?

Answer 27

IGF-1 is more potent than GH at stimulating chondrogenesis at epiphyseal growth plates in children

Question 28

What does mecasermin rinfabate have that mecasermin does not have?

Answer 28

Mecasermin rinfabate has rh-insulin-like growth factor binding protein 3 (rhIGFBP3)

Question 29

Which recombinant hormone has more side effects rhIGF or rhGH? Why?

Answer 29

rhGH has more side effects because it is more effective in inducing growth

Question 30

What are the side effects of rhIGF?

Answer 30

rhIGF causes hypoglycemia (take before or after a meal) and affects the liver (induces cyp450)

Question 31

Who should NOT be given rhIGF?

Answer 31

Children with cancer and patients with closed epiphyses should NOT be given rhIGF

Question 32

Hypersecretion of GH can cause gigantism/acromegaly, what usually causes hypersecretion of GH?

Answer 32

Pituitary adenoma of the somatotropes

Question 33

Is excess growth hormone common?

Answer 33

No...3 cases per million

Question 34

What kind of drugs can be used to treat hypersecretion of growth hormone?

Answer 34

Somatostatin (SSTR1-5) or dopamine (D2) analogs | GH receptor antagonist (newer)

Question 35

What is an example of a dopamine agonist used to treat gigantism/acromegaly? What somatostatin agonist?

Answer 35

Bromocriptine (dopamine agonist) | Octreotide (long-acting somatostatin analog)

Question 36

What is the name of the growth hormone receptor antagonist?

Answer 36

Pegvisomant

Question 37

What are the effects of pegvisomant? what are the side effects of pegvisomant?

Answer 37

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

Question 38

What needs to be considered when children are treated with cortisol?

Answer 38

Glucocorticoids antagonize growth promoting effects

Question 39

What effect does GH have on protein, mineral, carbohydrate, and fat metabolism?

Answer 39

Protein metabolism is increased Mineral metabolism is increased (greater bone density) Carbohydrate metabolism is decreased (diabetogenic) Fat metabolism is increased (energy)