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ANAT322 > Growth Hormone Dr. Stroh > Flashcards

Growth Hormone Dr. Stroh Flashcards

1
Q

how long is GH?

A

191 or 176 amino acids

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2
Q

what is GH’s function?

A

stimulate bone and muscle growth, protein synthesis, carbohydrate metabolism

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3
Q

what mediates carbohydrate metabolism? (what GH affects)

A

Insulin-like Growth Factor-1 (IGF-1)

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4
Q

what are GH’s target organs?

A

liver, growth plate, adipose tissue, muscle, lymphocytes, gonads

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5
Q

what gland releases GH?

A

anterior pituitary

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6
Q

more precisely how does it promote growth? (4 ways)

A

stimulate adipose cells to break down fat,
stimulates liver to break down glycogen (through IGF-1),
increases aa uptake, enhances cell proliferation

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7
Q

what are called the cells that make GH? what pourcentage of anterior pituitary cells do they make?

A

somatotropes
40%

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8
Q

more specifically where are somatotropes located?

A

lateral and dorsal pituitary

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9
Q

describe the GH gene complex

A

on chromosome 17q23, 5 ORFs, codes for 2 GHs

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10
Q

name 2 of the genes (ORFs) on the GH gene complex

A

placental GH (GHv) and placental lactogen (PL)

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11
Q

how is GH secreted in humans?

A

through 8-10 peaks over 24h, with one really big peak around bedtime

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12
Q

how is GH level controlled?

A

through secretion; a lot is made, not all is secreted

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13
Q

when during lifetime do we secrete the most GH?

A

puberty

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14
Q

what are the 2 levels at which GH is regulated?

A
  1. anterior pituitary through GHRH (+) and somatostatin (-)
  2. hypothalamus through GHRH neurons in arcuate nucleus regulated by somatostatin
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15
Q

on what do GHRH and SST act to regulate GH in the anterior pituitary?

A

somatotrophs

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16
Q

what are the somatostatin receptors on GHRH neurons?

A

sst1 and sst2

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17
Q

what happens to GH peaks at you get older? how does it affect sleep?

A

amount and amplitude of GH peaks decrease, and slow wave sleep decreases

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18
Q

what are the hypothalamic factors influencing GH secretion?

A

neuropeptides (GHRH, SST, ghrelin, NPY, galanin), and neurotransmitters (DA,NE, Epi, Ach)

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19
Q

what are the peripheral factors influencing GH secretion?

A

thyroid hormones, sex steroids (estrogens, androgens), glucocorticoids (cortisol), ghrelin, leptin, fatty acids, aa, glucose, IGF-1 feedback

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20
Q

what are the social behaviors factors influencing GH secretion?

A

sleep, exercise, nutrition, stress

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21
Q

what’s the other name for somatostatin?

A

somatotropin release-inhibiting factor SRIF

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22
Q

how long is the active GHRH gene? on what chromosome is it found?

A

44 amino acids from a 108 aa precursor
chromosome 20q11.1

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23
Q

where is GHRH expressed?

A

hypothalamus, mainly arcuate nucleus, also VMN

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24
Q

what are GHRH effect’s?

A

strongly increased production and release of GH in somatotrophs in anterior pituitary

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25
Q

how long is GHRH’s lifetime?

A

3-6 minutes super short

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26
Q

how long is somatostatin’s precursor? on what chromosome is it located? what does it yield?

A

116 amino acids; chromosome 3q28; can make SST-14 or SST-28

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27
Q

where is SST-28 found?

A

more in periphery (GI tract, pancreas, immune system)

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28
Q

where is SST the most expressed in the brain?

A

periventricular and arcuate nuclei in the hypothalamus

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29
Q

how does SST act?

A

inhibits GNRH secretion in arcuate nucleus and GH secretion in anterior pituitary somatotropes

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30
Q

in which other nucleus is SST also found?

A

POA, PVa, ah, VMN, DMN, Arc

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31
Q

how do GHRN and SST regulate GH?

A

GHRH and SST show a synchronous
and alternate pulse of release, respectively

32
Q

how does the periventricular nucleus regulate GH?

A

PVa secretes SST, TRH, CRH that act on GHRH neurons in ARC and SST is also released in ME

33
Q

how does the arcuate nucleus regulate GH?

A

ARC synthesizes GHRH that acts on PVa SST neurons

34
Q

what neuropeptide do arcuate neurons have receptors for related to GH?

A

GHRH AND SST

35
Q

where does the pulsatile activity of GH come from?

A

from negative feedback from plasma GH levels to SST PVa neurons

36
Q

how do GHRH and SST regulate GH in the anterior pituitary?

A

by activating / inhibiting adenylate cyclase (cAMP formation) through g-protein receptors.
GHRH increases cAMP levels, which activate PKA, which activates calcium channels and GH TFs -> increases GH

37
Q

what happens to people with GHRH receptor defects?

A

they still have pulsatile GH pulse, but very little is secreted

38
Q

describe GHSR

A

growth hormone secretagogue receptor is a 7 TM domains G-protein coupled receptor that activates phospholipase C

39
Q

what does GHS receptor activation cause?

A

stimulates release of GHRH in hypophyseal circulation and GH in general circulation

40
Q

where is ghrelin found?

A

in GI tract and arcuate nucleus

41
Q

how does Ghrelin act?

A

is stimulate GH release directly on anterior pituitary somatotropes and indirectly through hypothalamic arcuate nucleus GHRH neurons

42
Q

what is a big difference between GHRH and ghrelin?

A

ghrelin works as a peripheral hormone and has a longer half-life. Acts the same way as GHRH on anterior pituitary

43
Q

what causes severe short stature?

A

genetic GH deficiency usually due to GH gene defect, or to GHRH receptor defects in 10% of cases.
also called familial short stature

44
Q

what are the other causes of severe short stature?

A

GHR/signaling defect (rare)
IGF-I/IGF-I receptor defects (rarer)

45
Q

what is idiopathic short stature?

A

short stature in healthy people.
they respond normally to GH secretagogues

46
Q

what is special about some people with idiopathic short stature?

A

elevated GH and low IGF-I levels, suggesting tissue resistance to GH

47
Q

what is the only treatment for idiopathic short stature?

A

GH therapy. only 4-7 cm growth response

48
Q

which genes are researchers examining for heterozygous mutations in the coding and mutations/polymorphisms in the regulatory

A

GH, GHR, STAT5b, IGF, IGF-R

49
Q

what causes acromegaly?

A

excess pituitary GH synthesis and secretion caused by acidophilic adenoma of anterior pituitary

50
Q

what is gigantism?

A

when acromegaly (the pituitary adenoma) develops before puberty growth push

51
Q

what can the excess GH secretion in acromegaly be due to, other than a pituitary tumor?

A

GHRH oversecretion due to ectopic/hypothalamic tumor (only 5%)

52
Q

what causes the pituitary tumor in acromegaly/gigantism?

A

activating mutation in the somatotrope GHRH receptor protein

53
Q

what are physical features of acromegaly?

A

excess growth of soft tissues (nose, ears, hands, feet), greasy thick skin, coarse facial features

54
Q

what are invisible features of acromegaly?

A

insulin resistance/diabetes, high tri-glycerides in blood, arthritis, hypogonadism, hypertension, cardiomyopathies, colonic polyps

55
Q

what are the therapeutic approaches to acromegaly?

A

surgery (removing tumor), radiation, medications

56
Q

what are the medications for acromegaly?

A

long-acting oral chemical agents that suppress GH secretion (like somatostatin analogues) or that block GH receptor

57
Q

what is the problem with each acromegaly medication?

A

suppressing GH secretion: using dopaminergic agonists that aren’t specific enough
blocking GH receptor: low IGF-I

58
Q

what is somatopause? what causes it?

A

decrease in GH levels due to lower GHRH and pituitary responsiveness

59
Q

what are symptoms of somatopause?

A

increased BMI, thinner skin, decreased bone density, muscle weakness

60
Q

how can somatopause be treated?

A

exercise, sex/thyroid hormone treatment

61
Q

what is the risk with GH therapy?

A

promotes cell proliferation: could cause tumors
(high serum GH/IGF-I associated with increased breast, prostate, colorectal cancer)

62
Q

what are the 2 growth promoting factors

A

GH and IGF-I

63
Q

what is the predominant receptor subtype in the CNS? (present in Arc and ant pit)

A

Sst2a

64
Q

where are the other sst receptors found?

A

sst1: hypothalamus
sst5: anterior pituitary

65
Q

what are sst1, sst2a, sst5 involved in?

A

sst1, sst2A: mediate SST effect on GHRH arc neurons
sst2a, sst5: regulate GH in pituitary (present in all pituitary cells)

66
Q

more specifically where is sst1 highly expressed?

A

ventro-medial arcuate nucleus - on GHRH neurons!

67
Q

what did Dr. Stroh discovered about neuropeptides and their release?

A

they aren’t just distributed along the cell surface, they are associated with synapses

68
Q

at what timing were there the most sst1 receptors associated with synapses?

A

before the GH peak, there were 50% more

69
Q

at any given time, how much sst receptors are associated with synapses?

A

about half

70
Q

with what kind of synapses do sst1r associate with in Arc? what does it do and what does it mean?

A

with inhibitory symmetric synapses. inhibitory neuropeptide on inhibitory synapses = stimulation. suggests that Arc neurons can regulate their sensitivity to SST through GH cycle.

71
Q

we thought SST2r went to the TNG, but Dr stroh’s college foudn that it goes where?

A

in vesicular compartments close to TGN

72
Q

how did they find the GSVL that store sst2?

A

through GSV that stores Glut4 which acts similarly to sst2

73
Q

what molecule triggers GSVL to bring sst2 to cell surface?

A

CRF

74
Q

when are sst receptors internalized vs externalized?

A

internalized when GH is low, externalized when GH is high

75
Q

what is the double regulation of sst?

A

SST secretion AND SST receptor expression gets regulated throughout GH cycle

76
Q

what is colocalization?

A

neurons, ex GHRH neurons in arcuate nucleus, don’t only have one function or secrete only one thing. they have many functions

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