Growth Hormone Flashcards

1
Q

Growth hormone basics

A
  • Also called somatotrophin
  • Polypeptide hormone
  • Half life: 20 minutes
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2
Q

Excess of GH during childhood results in what?

A

Gigantism

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3
Q

Excess of GH during adulthood results in what?

A

Acromegaly

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4
Q

Deficiency of GH during childhood results in what?

A

Dwarfism

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5
Q

Regulation of GH secretion

A
  • Hypothal releases GHRH (positive mediator)
  • Hypothal can also release somatostatin (negative mediator)
  • Stomach and pancreas release ghrelin (positive mediator)
  • All activate G-Protein coupled receptors
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6
Q

Role of GHRH

A
  • Increases GH gene transcription
  • Promotes GH release
  • Stimulates production of GHRH receptor
  • Stimulates somatostatin release (negative feedback loop)
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7
Q

Role of somatostatin

A
  • Decreases GH pulse frequency and amplitude
  • No impact of GH synthesis
  • Inhibits GHRH release
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8
Q

Role of ghrelin

A
  • Stimulates hunger
  • Increase before meals and decrease after
  • Acts of growth hormone secretagogue receptor
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9
Q

Secretion of GH

A
  • Pulsatile
  • Primarily at night
  • Larger amplitude during puberty
  • Exercise can increase GH
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10
Q

Stimulation of GH secretion

A
  • Deep sleep
  • Exercise
  • Sex steroids
  • Fasting/hypoglycemia
  • Amino acids (arginine)
  • Stress
  • alpha-adrenergic agonists
  • Dopamine agonists
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11
Q

Inhibition of GH secretion

A
  • IGF-1
  • Obesity
  • Glucocorticoids
  • Hyperglycemia
  • Free FAs
  • GH
  • B-adrenergic agonists
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12
Q

GH activation of its receptor

A
  • Transmembrane receptor in cytokine receptor family
  • GH binding causes rearrangement of receptor dimer that activates JAK2
  • JAK2 phosphorylates/activates STAT transcription factors
  • STATs dimerize and translocate to the nucleus and act as transcription activators
  • Increased expression of CISH (a GH target gene)

-NO inherent tyrosine kinase receptor activity

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13
Q

Cause of short stature in pygmies

A

-Severe underexpression of GH receptor

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14
Q

GH regulation/effects

A
  • GH release by ant pit controlled by GHRH (arcuate nucleus) and somatostatin (PVN nucleus) from the hypothal’
  • GHRH stimulates Gs receptors, increases cAMP and Ca, PKA is activated and CREB phosphorylated causing pit-1 to upregulate GH and GHRH receptor.
  • Somatostatin inhibits AC via Gi receptors and lowers Ca.
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15
Q

Effects of GH

A
  • Postnatal longitudinal growth (indirect and direct)
  • Stimulates production of IGF-1 in liver and glucose production
  • Stimulates release and oxidation of FFAs in adipose tissues. Reduces lipoprotein lipase activity. Lipogenesis reduced.
  • Anabolic effects on skeletal musccle. Stimulates AA uptake and suppresses protein degradation.
  • Affects mood and behavior
  • Counteracts action of insulin on lipid and glucose metabolism
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16
Q

Effect of GH on bone

A
  • Supports differentiation of mesenchymal stem cells (prechondrocytes) into chondrocytes
  • IGF-1 induces clonal expansion and maturation
  • Synthesis of ECM proteins including type 2 collagen, hyaluronic acid, and mucopolysaccharides.
  • Combined effects from GH and IGF-1
17
Q

IGF-1

A
  • Production in liver stimulated by GH
  • Stimulates growth
  • Negative feedback to hypothalamus and pituitary to down-regulate GH secretion
  • Primary screening test when considering GH deficiency
18
Q

Signaling pathways activated by IGF-1

A
  • Dimerization of receptor leads to autophosphorylation
  • Recruits IRS-1 and Shc which are phosphorylated by IGF-1 receptor
  • Activates PI3K and the Ras/MAP kinase pathways that regulate transcription
19
Q

GH deficiency

A
  • Severe postnatal growth failure
  • Mutations in GH-1 gene, defect in hypothamo-pit function
  • Can treat with recombinant IGF-1 often
20
Q

Laron Syndrome

A
  • Growth hormone insensitivity
  • Mutation or deletion in GH receptor
  • Low IGF-1 concentration
  • Normal or elevated GH concentration
  • Treatable with rhIGF-1
  • Autosomal recessive
21
Q

Short stature in turner syndrome

A

-SHOX gene insufficiency