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Endo/Repro: Week 1 > Rose: GH and PRL > Flashcards

Rose: GH and PRL Flashcards

1
Q

What is a sommatotropic hormone?

A

GH

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2
Q

What is a mammotropic hormone?

A

PRL

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3
Q

What inhibits PRL?

A

DA

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4
Q

What stimulates GH?

A

GHRH

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5
Q

What inhibits GH?

A

GHIH= Somatostatin

DA

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6
Q

What does GHIH act through?

A

Gi-coupled receptor to decrease cAMP and activate K+ channels

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7
Q

Where are GHRH receptors located? What type of receptor is it?

A

somatotrophs

transmembrane G protein coupled

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8
Q

GH (somatotropin) is made by…

A

somatotropes

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9
Q

What is indicative of tissue levels of GH receptor?

A

Levels of GHBP which binds GH

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10
Q

How does GHBP affect GH?

A

Acts as a reservoir of growth hormone in plasma and may be a modulator/inhibitor of GH signaling.

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11
Q

What are transmembrane GH receptors on target cells?

A

Cytokine receptor that activates JAK/STAT secondary messenger signal transduction pathway

Hormone binding causes dimerization and internalization of complex

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12
Q

What are the target cells for GH?

A

Isoform of GHR is in nearly all cells

Liver produces Insulin-like growth factor-1 (IGF-1=somatomedin)

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13
Q

What are the final hormones mediating the GH axis?

A

GH

IGF-1

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14
Q

How does GH affect liver IGF-1 gene expression?

A

GH> stimulates IGF-1 gene expression>

IGF-1 is an EFFECTOR for growth

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15
Q

What happens if IGF-1 > GH?

A

stimulates chondrogenesis (growth) at epiphyseal growth plates in children

*(Growth promoting effects are antagonized by glucocorticoids - important in children being treated with cortisol.)

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16
Q

How are the diabetogenic properties of GH?

A

Increase circulating glu:
reduces tissue uptake of glucose
increases liver production of glucose

Decreases circulating glucose:
secondary insulin release

*GH increases the incidence of diabetes mellitus (insulin resistance is often observed in these patients)

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17
Q

GH can affect…

A

protein metabolism
mineral metabolism
carbohydrate metabolism
fat metabolism

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18
Q

What causes proportional dwarfism?

A

GH def in children caused by gene mutations in the GH axis

  1. Laron syndrome
  2. SHOX loss/point mutations
19
Q

What is laron syndrome? What is the mechanism?

A

A cause of dwarfism

autosomal recessive GH receptor variant with insensitivity to GH

*Underlying mechanism for short stature is at the RECEPTOR level

20
Q

What is the SHOX gene? What happens if you lose a copy?

A

short stature homeobox gene located on the X

Loss of SHOX copy: e.g., short stature with Turner’s syndrome(45, XO or Turner mosaicism ) is a chromosomal condition altering development in FEMALES. It is associated with loss of a single copy of the SHOX.

21
Q

What is observed in GH def in adults?

A

generalized obesity
reduced muscle mass
asthenia (reduced energy, weakness)
reduced cardiac output

22
Q

Why are random serum samples NOT useful in assessing GH def?

A

pulsatile pattern

23
Q

How is the insulin tolerance test used to dx GH def?

A

Insulin>
hypoglycemia>
stimulates adrenal glands to secrete cortisol and pituitary to secrete GH

**failure to respond to insulin suggests need for GH replacement
f

24
Q

What is hte glucagon test?

A

glucagon>
transient hyperglycemia>
hypoglycemia>
stimulates GH

  • safer than an insulin test
  • Failure to respond to insulin may suggest the need for glucocorticoid and growth hormone replacement
25
Q

GH is used therapeutically to tx hyposecretion syndromes in children such as:

A
  1. Hypopituitarism (decrease in one or more pituitary hormones)
    -most common pituitary hormone deficiency is GH
    -deficiency ≈1/4000 births
    hypoglycemia is an early sign - due to unopposed action of insulin
  2. Idiopathic short stature
  3. Turner Syndrome growth deficiency
  4. Other SHOX mutations
  5. Trauma
26
Q

What is the goal of GH therapy?

A

to maintain IGF-1 and IGFBP3 levels in mid-normal range for age and gender matched controls

27
Q

Where do GH preparations come from?

A

Recombinant human growth hormone (rhGH) preparations

Omnitrope, Nutropin, Norditropin, Genotropin, Siazen

28
Q

What are the SE of GH?

A
  1. Immune response- Abs
  2. Scoliosis during rapid growth
  3. diabetogenic
29
Q

What is an IGF def that is NOT responsive to GH?

A

Laron type dwarfism

30
Q

What is Laron type dwarfism?

A

Autosomal recessive

GH receptor variant which has WEAK binding to GH> Result is also low IGF-1 levels

Present at birth

31
Q

What rhIGF treaments are available?

A 
Mecasermin (Increlex) = rh IGF-1
Mecasermin rinfabate (Iplex) = complex of recombinant human rhIGF-1 plus rh-insulin-like growth factor binding protein-3 (IGFBP3)
32
Q

What is IGFBP3?

A

an IGF carrier protein

-provide stability and increase IGF-1 half-life
-stimulates growth during the first year but may not be enough to bring patients into the normal range
-not as effective as GH in children who can respond to growth hormone.
Net result: Fewer negative side effects than GH

33
Q

What are hte SE of rhIGF?

A

Hypoglycemia (administer immediately before or after a meal)
Liver effects: Increases cytochrome p450 - reduces the duration of drugs metabolized by that system - steroids, anticonvulsants

34
Q

Who should rhIGF not be given to?

A

Should not be given to children with cancer

Should not be given for growth promotion in patients with closed epiphyses.

35
Q

What are clnical features of GH hypersecretion?

A

Gigantism that can evolve to acromegaly

  • increased height, prominent lower jaw
  • enlarged hand w/ stubby fingers and foot
36
Q

Hypersecretion of GH in adults can lead to…

A

acromegaly

37
Q

What are sxs of acromegaly?

A

Lengthened jaw
Coarsened features
growth in hands and feet
Stubby fingers

38
Q

How does hypersecretion of GH cause gigantism/acromegaly?

A

timing of epiphyseal plates closure

39
Q

How do you dx GH hypersecretion?

A
  1. elevated IGF-1

2. Confirmed by elevated GH level 2 hr after glucose administration

40
Q

What is used to treat hypersecretion of GH?

A

Promotion of GHIH and DA

41
Q

What is bromocriptine?

A

DA agonist

42
Q

What is ocreotide?

A

long acting somatostatin analog (longer half lives, good for treating hypersecretory growth in adults w/ acromegaly)

43
Q

What is pegvisomant? Mechanism?

A

GH antagonist

blocks the hepatic GH receptor thereby prevent IGF-1 release

Reduced IGF-1 may increase GH

Endo/Repro: Week 1 (10 decks)

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