growth hormone biochemistry Flashcards

1
Q

what is the target organ of growth hormone?

A

bone and soft tissue

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2
Q

what type of hormone is growth hormone?

A

it is peptidal

protein because it is large

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3
Q

what are the hormones released from the hypothalamus?

A

Thyrotropin releasing hormone

Prolactin inhibiting hormone ( dopamine )

Growth hormone releasing hormone

Somatostatin ( Growth hormone inhibiting hormone )

Gonatotropin releasing hormone

corticotropin release hormone

Antidiuretic hormone / vasopressin

Oxytosin

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4
Q

describe the molecular structure of growth hormone?

A

single chain protein of 191 amino acids

Size approximately 22kDa

globular structure

Alpha helical structure

2 cysteine bridge

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5
Q

how will gh encourage growth?

A

Direct effect from GH

Indirect effect by IGF1 from liver and MUSCLES

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6
Q

what is the function of the 2 cysteine bridges?

A

stabilize the tertiary structure

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7
Q

under what influence is growth hormone released?

A

growth hormone releasing hormone secreted by HYPOTHALAMUS

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8
Q

in which signaling method will GHRH will work on somatotroph ?

A

G protein coupled n second messenger

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9
Q

describe the mechanism of GHRH?

A

binds to the receptor –> S subunit will get activated by GTP to become active G protein —> Alpha subunit will MOVE –> activates ADENYLATE CYCLASE —-> adenylate cyclase will increase CAMP –> CAMP will activate PKA –> short and long term effects

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10
Q

what are the short term of increased CAMP and pka in somatotroph cells?

A

increases calcium —-> Vesicles release GH

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11
Q

what are the long term effects of CAMP and pka in somatotroph cells?

A

increase dna expression and Synthesis of mra –> translation of GH

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12
Q

what is the signaling mechanism of GH?

A

Jak/stat pathway

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13
Q

describe the jak/stat pathway of GH?

A

growth hormone binds to the receptor —-> dimerization of inner part of the receptor —–> JAK kinase is activated —-> phophorylation —-> STATIN protein binds to the phosphate group —-> Increase GENE EXPRESSION AND TRANSLATION OF proteins including IGF1

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14
Q

what is JAK kinase?

A

type of tyrosine kinase

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15
Q

where is GH receptor present?

A

Liver, adipocytes , bone , cartilage, other cells

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16
Q

what are the 3 pathways JAK kinase can increase gene expression?

A

1- STAT pathway —>Stat binds to phosphate

2- MAPK pathway

3- PI3K, PKB pathway

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17
Q

what is the result growth hormone binding?

A

production Insulin growth factor 1 generation ( IGF1)

Alteration of glucose metabolism ( increase glucose lvl and decrease uptake )

modulation of cell proliferation genes

increase protein synthesis and decrease amino acid

Lipolysis ( all hormones will cause lipolysis except insulin )

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18
Q

how will GH causes most of its effect?

A

IGF1

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19
Q

which are the hormones are involved in growth?

A

IGF-1

thyroxine

cortisol

sex steroids

insulin

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20
Q

how is the release of GH is controlled?

A

Growth hormone releasing hormone GHRH

Growth hormone inhibitory hormone ( somatostatin )

IGF1 inhibits GHRH and GH and stimulate GHIH –> negative feedback hypothalamus

Ghrelin will stimulate release the GH and GHRH

GH will inhibit itself by Negative feedback

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21
Q

what are the examples gene transcribed by GH?

A

IGF1

alpha macroglobulin

serine protease inhibitors ( SPI )

ornithine decarboxylase

22
Q

what is the function IGF-1 ?

A

Insulin like effects

IGF-1 can regulate cell growth and development–> in nerve cells as well as DNA synthesis

23
Q

how is IGF1 circulating in the blood?

A

80% OF it is carried by IGFBP1

24
Q

along side the liver where is IGF1 produced?

A

cartilaginous cells –> in this case it will be paracrine hormone

Muscles

25
what is the mechanism of signaling used IGF1?
Receptor enzyme the receptor has tyrosine kinase in it similar to INSULIN
26
what will IGF1 do after binding to the receptor?
Increases cell proliferation --> visceral, muscle, bone growth Decrease apoptosis increase protein synthesis increase glucose metabolism
27
what is the effect of growth hormone on skeletal muscles?
inhibits the uptake of glucose by muscles --> inhibit GLYCOSIS increase amino acid transport for protein synthesis Increase FFA stimulates muscle growth energy expenditure
28
what is the effect of growth hormone effect on adipocytes?
1- FIRST insulin like effect 2- Followed by anti insulin effect 3- decreased glucose transport to adipocyte 4- Increase lipolysis 5- promotes fatty acid oxidation
29
how will gH cause lipolysis?
stimulate Hormone sensitive lipase
30
what is the result of fatty acid oxidation?
Acetly COA glycerol
31
what will happen to the acetly coa that came fatty acid oxidation?
Ketogenesis --> mainly in liver cells
32
what will happen to glycerol that came from fatty acid oxidation?
could be used as substrate for gluconeogenesis
33
what does GH do to glycolysis ?
since it increases Glucose lvl --> it has to inhibit glycolysis
34
when is GH level is not ordered?
it is not used for screening
35
when do we order GH levels?
signs and symptoms of excess or deficiency of growth hormone --> acromegaly . gigantism , dwarfism When x ray shows delayed bone development To measure success of hormone therapy To evaluate the pituitary function AS an additional test to EXCLUDE hypothyroidism as cause of non growing child
36
which hormone is required for growth after birth?
Thyroid
37
what are some points to consider we look at GH level?
Fasting GH level --> during fasting and hypoglycemia GH level is high and hyperglycemia inhibit GH secretion IGF1 level --> IGF1 revel mirror GH in both excess or deficiencies GH stimulation of suppression test --> in stimulation we make the patient fast and to suppress we INDUCE HYPERGLYCEMIA
38
when we wanna measure GH levels what is the best indicator and why?
IGF-1 because it is stable throughout the day and GH state changes throughout the day so it is not reliable
39
describe the process of GH suppression test?
- patient fast for 10-12 hours - withdraw blood to measure the base level of GH - Administer glucose to induce hyperglycemia - withdraw samples in different intervals - check GH levels In normal people Glucose should inhibit GH secretion
40
what does it indicate when glucose cannot suppress GH?
it indicates Acromegaly or gigantism
41
what is the gold standard for diagnosing acromegaly?
OGTT with GH measurement
42
what is OGTT and how it works?
Oral glucose tolerance tests we induce hyperglycemia ---> if GH is lowered --> normal --> If not acromegaly
43
how do you diagnose GH deficiency?
Stimulation test
44
describe the stimulation test
- patent fasts for 10-12 hours - Administer Insulin CAREFULLY to induce even more hypoglycemia - Withdraw blood at timed intervals - measure GH in the samples in normal people GH should increase
45
what are other stimulation of GH besides hypoglycemia?
clonidine arginine
46
what does it indicate when GH is low and IGF 1 is low ?
problem in the GH itself , pituitary problem
47
what is the treatment when GH is the problem?
Recombinant GH
48
what does it indicate when GH is high but IGF1 is not?
1- patient has GH resistance 2- GH receptors are not working due to mutation --> laron syndrome 3- cells cannot produce IGF-1 --> pygmies of africa / levi lorain dwarfism
49
what is the treatment in case of IGF1 deficiency?
administer recombinant IGF-1
50
what is the method of administering GH or IGF1?
injection either IV or IM or Subcutaneous Not oral cuz it will get digested by GIT ( peptidal hormone , water soluble )
51
how is human growth hormone recombinant produced?
genetically engineered bacteria manufactured by RECOMBINANT DNA technology ( E coli )