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Endo > Growth Hormone > Flashcards

Growth Hormone Flashcards

Wk 6

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
Q

What are the two types of IGF?

A

IGF-I and IGF II

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26
Q

What is IGF-II essential to?

A

embryonic development

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27
Q

GH is a trophic hormone- what does it stimulate?

A

The secretion of IGF-1

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28
Q

What are the main roles of IGF-1?

A

Skeletal and Cartlidge growth

Acts on target via IGF receptor

Mediates growth-promoting effects of GH

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29
Q

what are the receptors of IGF-II?

A

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

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30
Q

Where is IGF-II expressed?

A

in early embryonic and foetal development in a wide variety of somatic tissues.

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31
Q

what are the functions of IGF-II

A

Fetal growth

Crucial factor of cell proliferation, migration, differentiation and survival regulation.

Growth promoting function during embryonic development and placental growth

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32
Q

why is it difficult to attribute specific roles of growth hormone for biological effects? (direct actions)

A

it uses a signal transducer and activator of transcription (STAT) to induce IGF for most direct actions.

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33
Q

What are the indirect effects on growth by GH?

A

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

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34
Q

What is the nature of GH secretion?

A

episodic and exhibits a diurnal (daily) rhythm. 2/3 produced at night time

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35
Q

what are the primary controllers of GH regulation

A

Hypothalamic factors: GHRH and GHIH

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36
Q

What is the short and long term effect of GHRH on GH?

A

Short term: increased GH release

Long term: increased GH production

37
Q

Where does GHRH come from?

A

ventromedial nucleus of the hypothalamus (VMH)

38
Q

What is the general role of GHRH?

A

Stimulates the synthesis and secretion of GH.

39
Q

What does GHIH respond to, to inhibit GH?

A

GHRH or other stimulatory factor low BG)

40
Q

What is the role of IGF-1 in regulating GH secretion?

A

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
Q

What is hyposectertion of GH most significant in?

A

children but is uncommon

41
Q

What happens to adults with GH absence?

A

increased body fat and loss of muscle strength

42
Q

What are the potential causes of GH deficiency?

A

GH secretion reduced

GH-stimulated IGF production decreased

Deficient IGF action

43
Q

Why do people with hyposecretion of GH have obesity?

A

Lost the ability for GH induced lipolysis

44
Q

What occurs if GH deficiency is panhypopituitary?

A

may not mature sexually and infertile

45
Q

What are the metabolic abnormalities for people with dwarfism?

A

Gn hormone defiency

Metabolic abnormalities= hypoglycemia,

46
Q

What are the signs and symptoms of Laron Dwarfism?

A

reduced muscle strength and endu, hypoglycemia, delayed puberty in infancy, small genitals, short limbs and obesity

47
Q

What is the presentation and cause of Laron Dwafism

A

GH receptors are unresponsive due to mutation on GH receptor gene

48
Q

What happens to GH receptors, GHBP and GH in Laron dwarfism

A

decreased GH receptors and GHBP but normal/elevated GH

49
Q

Describe the plasma GH, baseline serum GHBP and IGF-1 levels in African pygmies.

A

Normal plasma GH levels but low levels of baseline serum GH-binding protein (GHBP) and IGF-1

50
Q

What are the clinical conditions of African Pygmies?

A

Lack pubertal serum IGF-1 surge and growth spurt

51
Q

What are the causes of Giantism?

A

Excessive GH before puberty – increased GH before epiphyseal plates are fused = increased height

Acidophilic tumours

52
Q

What are the signs and symptoms of giantism?

A

Increased body weight, body tissues grow rapidly, hyperglycaemia (glucose intolerance), hyperinsulinemia, eventual development of panhypopituitarism(tumour) and cardiovascular problems (viscera increase in size)

53
Q

What is the pathophysiology of giantism?

A

beta cells of pancreas degenerate

54
Q

What is the cause of Acromegaly?

A

excessive secretion after epiphyses close

55
Q

What is the pathophysiology of acromegaly?

A

Cartlidge and membranous bones grow but can result in gross deformities. Soft tissue growth= cardiovascular problems (cardiac hypertrophy)

56
Q

What are the symptoms of Acromegaly?

A

change in facial apperance, headaches, goitre, deep voice, tiredness, weight gain, excessive sweating, amenorrhoea, galactorrhoea and increased glove/hat size.

57
Q

What are the signs of acromegaly?

A

prognathism, interdental separation, large tongue, thick greasy skin, spade like hands and feet and carpal tunnel; syndrome.

58
Q

What happens to a patient with a pituitary tumour secreting GH after given a glucose drink?

A

GH not suppressed by glucose and blood GH still measurable after an hr.

59
Q

What is GH most important for and what is it influenced by in this role?

A

GH is the most important hormone for postnatal growth. It is influenced by TH, androgens, oestrogens, glucocorticoids and insulin.

60
Q

What is cessation growth due to?

A

closure of epiphyses by estrogens

61
Q

what is the difference between IGF-1 and IGF-2 in terms of action?

A

IGF-1 acts mostly on bone, cartilage and smooth muscle

IGF-2 has most profound impact on embryonic development

62
Q

What is GH stored in after protein synthesis?

A

granules

63
Q

Describe GH in circulation.

A

GH binds to Growth Hormone Binding Protein (GHBP) which is a growth hormone receptor.

64
Q

What is Dimerisation?

A

The process of joining two identical or similar molecules (e.g. proteins)

65
Q

What is the impact of GH on Fat Metabolism?

A

increased utilisation of fats (as is glucose sparing) and enhanced lipolysis

66
Q

What type of hormones are hypoglycemics hormone?

A

GH and thyroid hormone

67
Q

What stimulates GH secretion?

A

increased amino acid levels
decreased glucose and fatty acids in the blood

exercise
healthy stressors

68
Q

decribe the mechanism of action when GH binds to JAK STAT pathway.

A

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
Q

What is the effect of GH on muscles?

A

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
Q

What are the summarised impacts of GH on bones?

A

Increased collagen-type 1 production

Increased proteoglycans

Increased activity of osteoblasts and osteoclasts = enhanced endochondral ossification (increased bone mass)

71
Q

what are the summarised impacts of GH on cartridge?

A

Increased size, differentiation, and proliferation of chondrocytes

Differentiation= conversion into bone via intestinal growth = increased length of bone

72
Q

What is the impact of GH on the liver?

A

Stimulates glucogenesis = increased BGL from glucose from non-carbohydrate source.

73
Q

What is the impact of GH on glucose?

A

It allows for an increase in glucose without using carbohydrate sources. This occurs via lipolysis

74
Q

Describe the mechanism of action for lipolysis.

A

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
Q

Why does the hypersecretion of GH result in hyperglycemia?

A

increasing endogenous glucose production and decreasing peripheral glucose disposal in muscl

76
Q

what is hyperinsulinemia

A

high amounts of insulin

increases risk of type-2 diabetes

77
Q

what is type-2-diabetes

A

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
Q

what is the difference between giantaism and acromegaly?

A

Acromegaly is the excessive secretion AFTER epiphyses close whilst Giantasim is BEFORE it closes

79
Q

What does both high and low GH result in?

A

Hyperglycemia.

80
Q

How does high GH result in hyperglycemia?

A

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
Q

What does insulin do?

A

breaks down glucose to turn it into energy

82
Q

How does low GH result in hyperglycemia?

A

There is a decrease in insulin production which mimics type-1 diabetes resulting in an increase in glucose

83
Q

when does the epiphyses close? What is the impact of this?

A

After Puberty,

if have hypersecretion of GH before puberty = giantism if it is after = acromelgy

84
Q

why do patients with hypersecretion of GH get increased blood pressure?

A
85
Q

When does IGF peak and why?

A

During puberty

86
Q

what is puberty due to?

A

GH, andorgens and estrogens

87
Q

When are the two periods of rapid growth

A

infancy and late puberty

88
Q

when does a growth spurt occur for girls?

A

Earlier then boys

Endo (14 decks)

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