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Growth Hormone Flashcards

Wk 6 (89 cards)

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1
Q

What is the structure of GH?

A

191 amino acids in a straight-chained polypeptide.

2 internal disulfide bridges

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2
Q

What is GH closely related to and why?

A

prolactin- they have a common stem cell

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3
Q

What is GH synthesised by?

A

somatotrophs (acidophilic cells)

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4
Q

which cell type is the largest of the anterior pituitary?

A

somatotrophs

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5
Q

Where is GH expressed?

A

outside of the pituitary gland: brain, immune cells, reproductive tract and GIS

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6
Q

What receptor family does GH receptor belong to and what signal pathway does this connect it to?

A

Member of cytokine-GH-PRL-erythropoietin family

Linked to JAK-STAT signalling pathway

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7
Q

What type of hormone does GH function as in adults?

A

A metabolic hormone

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8
Q

Describe the impact of GH on Growth

A

GH causes growth of all tissues.

Increased: size of cells, mitosis and differentiation of cells

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9
Q

What are the metabolic effects of GH?

A

Increased rate of protein synthesis
* Increased mobilization of fatty acids from adipose tissue
* Increased free fatty acids in the blood
* Increased use of fatty acids for energy
* Decreased rate of glucose utilization throughout the body

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10
Q

Due to its effects on protein metabolism- what does GH cause the increase of?

A

lean body mass and increased organ size

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11
Q

What is the role of IGF-1

A

Mediates GH Protein anabolism

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12
Q

What is the role of GH on protein metabolism?

A

Increases uptake of amino acids and stimulates synthesis of DNA, RNA and proteins

Reduces protein oxidation

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13
Q

What does GH do in adipocytes?

A

Inhibits differentiation, reduces triglyceride accumulation and stimulates lipolysis and fat oxidation

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14
Q

What is the impact of GH administration on fat metabolism?

A

serum fatty acid levels rise = more fats used for energy production

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15
Q

What is ketosis?

A

excess mobilization of fat

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16
Q

When is the action of fat metabolism important?

A

during a fasted state when Gh is enhanced = partitioning of fuel utilisation towards fat

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17
Q

What does GH cause in carbohydrate metabolism?

A

insulin resistance and decreased glucose uptake and utilization by the target.

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18
Q

What is needed for correct pancreatic function and insulin secretion

A

normal levels of GH

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19
Q

What does excessive insulin secretion from excessive GH cause?

A

damage to pancreatic beta cells

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20
Q

What is needed for the growth-promoting action of growth hormone?

A

Adequate insulin activity

Adequate availability of carbohydrates

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21
Q

How are bones formed via GH?

A
  • GH targets chondrocytes that are cartilage-forming cells that generate cartilage matrix
    that subsequently becomes calcified
  • Osteoblasts migrate into the calcified matrix resulting in bone formation
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22
Q

How does GH exert its growth pormoting effects?

A

via peptide mediators: Insulin-like growth factors or somatomedins

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23
Q

Where are IGF’s produced?

A

in the liver, Cartlidge and most GH taret cells

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24
Q

what does IGF’s do?

A

Mediate GH action on Cartlidge and bone growth

Regulate cellular proliferation, differentiation and metabolism

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25
What are the two types of IGF?
IGF-I and IGF II
26
What is IGF-II essential to?
embryonic development
27
GH is a trophic hormone- what does it stimulate?
The secretion of IGF-1
28
What are the main roles of IGF-1?
Skeletal and Cartlidge growth Acts on target via IGF receptor Mediates growth-promoting effects of GH
29
what are the receptors of IGF-II?
Mannose-6 phosphate cell surface, glycoprotein receptors IGF2 can also bind to different signaling receptors, such as the IGF-1 type 1 receptor (IGF1R) and the insulin receptor, but with lower affinity
30
Where is IGF-II expressed?
in early embryonic and foetal development in a wide variety of somatic tissues.
31
what are the functions of IGF-II
Fetal growth Crucial factor of cell proliferation, migration, differentiation and survival regulation. Growth promoting function during embryonic development and placental growth
32
why is it difficult to attribute specific roles of growth hormone for biological effects? (direct actions)
it uses a signal transducer and activator of transcription (STAT) to induce IGF for most direct actions.
33
What are the indirect effects on growth by GH?
Promotes growth of bones and visceral organs It's administration increases skeletal and visceral growth Increased Cartlidge growth, long bone length and periosteal growth Most mediated by IGF-1
34
What is the nature of GH secretion?
episodic and exhibits a diurnal (daily) rhythm. 2/3 produced at night time
35
what are the primary controllers of GH regulation
Hypothalamic factors: GHRH and GHIH
36
What is the short and long term effect of GHRH on GH?
Short term: increased GH release Long term: increased GH production
37
Where does GHRH come from?
ventromedial nucleus of the hypothalamus (VMH)
38
What is the general role of GHRH?
Stimulates the synthesis and secretion of GH.
39
What does GHIH respond to, to inhibit GH?
GHRH or other stimulatory factor low BG)
40
What is the role of IGF-1 in regulating GH secretion?
high IGF-1 in blood creates a negative feedback loop that suppresses the somatotrophs to reduce production of GH and stimulates the release of GHIH from hypothalamus.
41
What is hyposectertion of GH most significant in?
children but is uncommon
41
What happens to adults with GH absence?
increased body fat and loss of muscle strength
42
What are the potential causes of GH deficiency?
GH secretion reduced GH-stimulated IGF production decreased Deficient IGF action
43
Why do people with hyposecretion of GH have obesity?
Lost the ability for GH induced lipolysis
44
What occurs if GH deficiency is panhypopituitary?
may not mature sexually and infertile 
45
What are the metabolic abnormalities for people with dwarfism?
Gn hormone defiency Metabolic abnormalities= hypoglycemia,
46
What are the signs and symptoms of Laron Dwarfism?
reduced muscle strength and endu, hypoglycemia, delayed puberty in infancy, small genitals, short limbs and obesity
47
What is the presentation and cause of Laron Dwafism
GH receptors are unresponsive due to mutation on GH receptor gene
48
What happens to GH receptors, GHBP and GH in Laron dwarfism
decreased GH receptors and GHBP but normal/elevated GH
49
Describe the plasma GH, baseline serum GHBP and IGF-1 levels in African pygmies.
Normal plasma GH levels but low levels of baseline serum GH-binding protein (GHBP) and IGF-1
50
What are the clinical conditions of African Pygmies?
Lack pubertal serum IGF-1 surge and growth spurt
51
What are the causes of Giantism?
Excessive GH before puberty – increased GH before epiphyseal plates are fused = increased height Acidophilic tumours
52
What are the signs and symptoms of giantism?
Increased body weight, body tissues grow rapidly, hyperglycaemia (glucose intolerance), hyperinsulinemia, eventual development of panhypopituitarism (tumour) and cardiovascular problems (viscera increase in size) 
53
What is the pathophysiology of giantism?
beta cells of pancreas degenerate
54
What is the cause of Acromegaly?
excessive secretion after epiphyses close
55
What is the pathophysiology of acromegaly?
Cartlidge and membranous bones grow but can result in gross deformities. Soft tissue growth= cardiovascular problems (cardiac hypertrophy) 
56
What are the symptoms of Acromegaly?
change in facial apperance, headaches, goitre, deep voice, tiredness, weight gain, excessive sweating, amenorrhoea, galactorrhoea and increased glove/hat size.
57
What are the signs of acromegaly?
prognathism, interdental separation, large tongue, thick greasy skin, spade like hands and feet and carpal tunnel; syndrome.
58
What happens to a patient with a pituitary tumour secreting GH after given a glucose drink?
GH not suppressed by glucose and blood GH still measurable after an hr.
59
What is GH most important for and what is it influenced by in this role?
GH is the most important hormone for postnatal growth. It is influenced by TH, androgens, oestrogens, glucocorticoids and insulin.
60
What is cessation growth due to?
closure of epiphyses by estrogens
61
what is the difference between IGF-1 and IGF-2 in terms of action?
IGF-1 acts mostly on bone, cartilage and smooth muscle IGF-2 has most profound impact on embryonic development
62
What is GH stored in after protein synthesis?
granules
63
Describe GH in circulation.
GH binds to Growth Hormone Binding Protein (GHBP) which is a growth hormone receptor.
64
What is Dimerisation?
The process of joining two identical or similar molecules (e.g. proteins)
65
What is the impact of GH on Fat Metabolism?
increased utilisation of fats (as is glucose sparing) and enhanced lipolysis
66
What type of hormones are hypoglycemics hormone?
GH and thyroid hormone
67
What stimulates GH secretion?
increased amino acid levels decreased glucose and fatty acids in the blood exercise healthy stressors
68
decribe the mechanism of action when GH binds to JAK STAT pathway.
GH binds to a Tyrosine Kinase like receptor --> phosphorylation of amino acids --> activates JAK enzyme (phosphorylates) --> produces Signal transducer activator of transcription (STAT) --> binds to gene sequence of DNA --> transcription of mRNA --> produces IGF-1 protein
69
What is the effect of GH on muscles?
GH binds to receptor on muscle cell which activates signal pathway to produce proteins --> phosphorylates amino acid channels to allow them to enter --> amino acids enter muscle.
70
What are the summarised impacts of GH on bones?
Increased collagen-type 1 production Increased proteoglycans Increased activity of osteoblasts and osteoclasts = enhanced endochondral ossification (increased bone mass)
71
what are the summarised impacts of GH on cartridge?
Increased size, differentiation, and proliferation of chondrocytes Differentiation= conversion into bone via intestinal growth = increased length of bone
72
What is the impact of GH on the liver?
Stimulates glucogenesis = increased BGL from glucose from non-carbohydrate source.
73
What is the impact of GH on glucose?
It allows for an increase in glucose without using carbohydrate sources. This occurs via lipolysis
74
Describe the mechanism of action for lipolysis.
GH binds to a receptor on adipose tissue --> activates hormone-sensitive lipase --> break down triglycerides ( fatty acids and 1 glycerol) --> Glycerol is used in glucogenesis to make more glucose via lipolysis (glucose-sparing reaction).
75
Why does the hypersecretion of GH result in hyperglycemia?
increasing endogenous glucose production and decreasing peripheral glucose disposal in muscl
76
what is hyperinsulinemia
high amounts of insulin increases risk of type-2 diabetes
77
what is type-2-diabetes
defective insulin secretion by pancreatic β-cells cells don't respond normally to insulin; this is called insulin resistance. Your pancreas makes more insulin to try to get cells to respond. Eventually, your pancreas can't keep up, and your blood sugar rise
78
what is the difference between giantaism and acromegaly?
Acromegaly is the excessive secretion AFTER epiphyses close whilst Giantasim is BEFORE it closes
79
What does both high and low GH result in?
Hyperglycemia.
80
How does high GH result in hyperglycemia?
puts the body in a diabetogenic state which puts the body in a type-2-like-diabetic state. This makes tissues less sensitive to insulin causing an increase in glucose.
81
What does insulin do?
breaks down glucose to turn it into energy
82
How does low GH result in hyperglycemia?
There is a decrease in insulin production which mimics type-1 diabetes resulting in an increase in glucose
83
when does the epiphyses close? What is the impact of this?
After Puberty, if have hypersecretion of GH before puberty = giantism if it is after = acromelgy
84
why do patients with hypersecretion of GH get increased blood pressure?
85
When does IGF peak and why?
During puberty
86
what is puberty due to?
GH, andorgens and estrogens
87
When are the two periods of rapid growth
infancy and late puberty
88
when does a growth spurt occur for girls?
Earlier then boys

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