Growth Hormone Flashcards
1
Q
Growth hormone basics
A
- Also called somatotrophin
- Polypeptide hormone
- Half life: 20 minutes
2
Q
Excess of GH during childhood results in what?
A
Gigantism
3
Q
Excess of GH during adulthood results in what?
A
Acromegaly
4
Q
Deficiency of GH during childhood results in what?
A
Dwarfism
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
6
Q
Role of GHRH
A
- Increases GH gene transcription
- Promotes GH release
- Stimulates production of GHRH receptor
- Stimulates somatostatin release (negative feedback loop)
7
Q
Role of somatostatin
A
- Decreases GH pulse frequency and amplitude
- No impact of GH synthesis
- Inhibits GHRH release
8
Q
Role of ghrelin
A
- Stimulates hunger
- Increase before meals and decrease after
- Acts of growth hormone secretagogue receptor
9
Q
Secretion of GH
A
- Pulsatile
- Primarily at night
- Larger amplitude during puberty
- Exercise can increase GH
10
Q
Stimulation of GH secretion
A
- Deep sleep
- Exercise
- Sex steroids
- Fasting/hypoglycemia
- Amino acids (arginine)
- Stress
- alpha-adrenergic agonists
- Dopamine agonists
11
Q
Inhibition of GH secretion
A
- IGF-1
- Obesity
- Glucocorticoids
- Hyperglycemia
- Free FAs
- GH
- B-adrenergic agonists
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
13
Q
Cause of short stature in pygmies
A
-Severe underexpression of GH receptor
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.
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
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
