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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
how long is GHRH's lifetime?
3-6 minutes super short
26
how long is somatostatin's precursor? on what chromosome is it located? what does it yield?
116 amino acids; chromosome 3q28; can make SST-14 or SST-28
27
where is SST-28 found?
more in periphery (GI tract, pancreas, immune system)
28
where is SST the most expressed in the brain?
periventricular and arcuate nuclei in the hypothalamus
29
how does SST act?
inhibits GNRH secretion in arcuate nucleus and GH secretion in anterior pituitary somatotropes
30
in which other nucleus is SST also found?
POA, PVa, ah, VMN, DMN, Arc
31
how do GHRN and SST regulate GH?
GHRH and SST show a synchronous and alternate pulse of release, respectively
32
how does the periventricular nucleus regulate GH?
PVa secretes SST, TRH, CRH that act on GHRH neurons in ARC and SST is also released in ME
33
how does the arcuate nucleus regulate GH?
ARC synthesizes GHRH that acts on PVa SST neurons
34
what neuropeptide do arcuate neurons have receptors for related to GH?
GHRH AND SST
35
where does the pulsatile activity of GH come from?
from negative feedback from plasma GH levels to SST PVa neurons
36
how do GHRH and SST regulate GH in the anterior pituitary?
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
what happens to people with GHRH receptor defects?
they still have pulsatile GH pulse, but very little is secreted
38
describe GHSR
growth hormone secretagogue receptor is a 7 TM domains G-protein coupled receptor that activates phospholipase C
39
what does GHS receptor activation cause?
stimulates release of GHRH in hypophyseal circulation and GH in general circulation
40
where is ghrelin found?
in GI tract and arcuate nucleus
41
how does Ghrelin act?
is stimulate GH release directly on anterior pituitary somatotropes and indirectly through hypothalamic arcuate nucleus GHRH neurons
42
what is a big difference between GHRH and ghrelin?
ghrelin works as a peripheral hormone and has a longer half-life. Acts the same way as GHRH on anterior pituitary
43
what causes severe short stature?
genetic GH deficiency usually due to GH gene defect, or to GHRH receptor defects in 10% of cases. also called familial short stature
44
what are the other causes of severe short stature?
GHR/signaling defect (rare) IGF-I/IGF-I receptor defects (rarer)
45
what is idiopathic short stature?
short stature in healthy people. they respond normally to GH secretagogues
46
what is special about some people with idiopathic short stature?
elevated GH and low IGF-I levels, suggesting tissue resistance to GH
47
what is the only treatment for idiopathic short stature?
GH therapy. only 4-7 cm growth response
48
which genes are researchers examining for heterozygous mutations in the coding and mutations/polymorphisms in the regulatory
GH, GHR, STAT5b, IGF, IGF-R
49
what causes acromegaly?
excess pituitary GH synthesis and secretion caused by acidophilic adenoma of anterior pituitary
50
what is gigantism?
when acromegaly (the pituitary adenoma) develops before puberty growth push
51
what can the excess GH secretion in acromegaly be due to, other than a pituitary tumor?
GHRH oversecretion due to ectopic/hypothalamic tumor (only 5%)
52
what causes the pituitary tumor in acromegaly/gigantism?
activating mutation in the somatotrope GHRH receptor protein
53
what are physical features of acromegaly?
excess growth of soft tissues (nose, ears, hands, feet), greasy thick skin, coarse facial features
54
what are invisible features of acromegaly?
insulin resistance/diabetes, high tri-glycerides in blood, arthritis, hypogonadism, hypertension, cardiomyopathies, colonic polyps
55
what are the therapeutic approaches to acromegaly?
surgery (removing tumor), radiation, medications
56
what are the medications for acromegaly?
long-acting oral chemical agents that suppress GH secretion (like somatostatin analogues) or that block GH receptor
57
what is the problem with each acromegaly medication?
suppressing GH secretion: using dopaminergic agonists that aren't specific enough blocking GH receptor: low IGF-I
58
what is somatopause? what causes it?
decrease in GH levels due to lower GHRH and pituitary responsiveness
59
what are symptoms of somatopause?
increased BMI, thinner skin, decreased bone density, muscle weakness
60
how can somatopause be treated?
exercise, sex/thyroid hormone treatment
61
what is the risk with GH therapy?
promotes cell proliferation: could cause tumors (high serum GH/IGF-I associated with increased breast, prostate, colorectal cancer)
62
what are the 2 growth promoting factors
GH and IGF-I
63
what is the predominant receptor subtype in the CNS? (present in Arc and ant pit)
Sst2a
64
where are the other sst receptors found?
sst1: hypothalamus sst5: anterior pituitary
65
what are sst1, sst2a, sst5 involved in?
sst1, sst2A: mediate SST effect on GHRH arc neurons sst2a, sst5: regulate GH in pituitary (present in all pituitary cells)
66
more specifically where is sst1 highly expressed?
ventro-medial arcuate nucleus - on GHRH neurons!
67
what did Dr. Stroh discovered about neuropeptides and their release?
they aren't just distributed along the cell surface, they are associated with synapses
68
at what timing were there the most sst1 receptors associated with synapses?
before the GH peak, there were 50% more
69
at any given time, how much sst receptors are associated with synapses?
about half
70
with what kind of synapses do sst1r associate with in Arc? what does it do and what does it mean?
with inhibitory symmetric synapses. inhibitory neuropeptide on inhibitory synapses = stimulation. suggests that Arc neurons can regulate their sensitivity to SST through GH cycle.
71
we thought SST2r went to the TNG, but Dr stroh's college foudn that it goes where?
in vesicular compartments close to TGN
72
how did they find the GSVL that store sst2?
through GSV that stores Glut4 which acts similarly to sst2
73
what molecule triggers GSVL to bring sst2 to cell surface?
CRF
74
when are sst receptors internalized vs externalized?
internalized when GH is low, externalized when GH is high
75
what is the double regulation of sst?
SST secretion AND SST receptor expression gets regulated throughout GH cycle
76
what is colocalization?
neurons, ex GHRH neurons in arcuate nucleus, don't only have one function or secrete only one thing. they have many functions

ANAT322 (10 decks)

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