Growth hormone Flashcards
1
Q
what is growth hormone
A
a single chain polypeptide
191 amino acids 22kDa Inhumans
2
Q
what hormones does growth hormone have high structural homology with
A
PL and PRL
3
Q
is GH universal across species
A
no - highly specifies specific. Must use hGH for treating human deficiencies
4
Q
how does GH circulate
A
in plasma bound to GH binding protein
5
Q
half-life of GH
A
~50 minutes = relatively long
6
Q
when do levels of GH rise
A
puberty
7
Q
when does GH peak
A
adulthood/maturity
8
Q
where is GH synthesised
A
anterior pituitary
9
Q
where is GH secreted
A
anterior pituiatry
10
Q
what stimulates GH secretion
A
GHRH and ghrelin
11
Q
what inhibit GH secretion
A
somatostatin
12
Q
when does maximum GH secretion occur
A
during sleep
13
Q
gender differences of GH
A
women secrete ~3 times more GH per day
14
Q
GH receptor
A
cytokine family
widely expressed in most cells
15
Q
what happens when GH binds to GHR
A
causes the GHR to dimerise and activates the JAK2/STAT signalling cascade
16
Q
GHR knockout mice
A
no expression of GHR
Severe post natal growth retardation
no change at birth weight
still some growth, probs through insulin
17
Q
what kind of growth retardation occurs in knockout GHR mice
A
proportionate dwarfism and delayed puberty
18
Q
how does growth occur in GHR knockout mice
A
probably insulin signalling
19
Q
GH has a direct effect on growth
A
FALSE
20
Q
GH has an indirect effect on growth
A
TRUE
21
Q
how does GH stimulate growth
A
via secretion of IGF-1
22
Q
IGF-1
A
insulin like growth factor
23
Q
what stimulates secretion of IGF-1
A
GH
24
Q
what does IGF-1 stimulate
A
growth
25
where is IGF-1 secreted
liver
26
what triggers secretion of IGF-1 from the liver
GH binding to GHR
27
how des IGF-1 travel
in plasma bound to proteins, there are at least 6 different IGF-1 binding proteins
28
half life of IGF-1
10 minutes
29
how is half life of IGF-1 increased
binding it IGF-1 binding proteins, increases to 3 hours
30
when does IGF-1 have half life of 3 hours
when bound to IGF1 binding proteins
31
how does IGF-1 work
- binds to the cell surface of IGF-1 receptors
- increases protein synthesis
- cartilage formation and bone growth
- increases growth of all organs
32
GHRH
growth hormone releasing hormone
33
where is GHRH released
ARC nucleus in the hypothalmus
34
where is the ARC nucleus
hypothalamus
35
where does GHRH go
released from ARC
| travels in portal system to anterior pituitary somatotropin to stimulate GH
36
What does GHRH stimulate
GH
37
what has a similar effect to GHRH
ghrelin
38
what happens in the JAK/STAT cascade
STAT dimers drive the IGF-1 gene transcription and translation
39
what drives the transcription and translation of IGF-1
JAK/STAT signallig cascade
40
what happens when IGF-1 reaches receptor cells e.g bone
undergoes signal transduction cascades through receptor activation = growth
41
what is the negative feedback of GH
IGF-1 released from the liver binds to receptors on anterior pituitary somatotropin which inhibits GH secretion
42
how does bone growth occur
activation of cartilage growth plates located between shaft and head
43
proper name of growth plates
epiphyseal plates
44
where are epiphyseal plates located
between the shaft and the head
45
how does IGF-1 effect bone growth
induces formation of new cells that cause the shaft to increase in length at both ends
46
when is ossification complete
~25 years old
47
how do we know IGF-1 mediates growth promoting effects of GH
mice
IGF-1 knockout = severe growth retardation
wt and knockout same weight at birth
similar traits to GHR knockout. Both have no IGF-1
48
What kind of receptor is IGF-1 receptor
tyrosine kinase
| 4 subunits; 2 alpha outside cell, 2 beta transmembrane
49
what receptor is IGF1R similar to
insulin receptor
50
where does IGF-1 bind to IGF1R
extracellular domain - alpha
51
how are the alpha and beta subunits of IGF1 R bound to eachother
disulphide bonds // cystein residues
52
what does it mean that the IGF1 R is kinase
it has enzyme activity
53
what is the enzyme activity of the IGF1 R
when IGF1 binds, induces a conformational change
tyrosine kinase within beta subunits becomes activated
autophosphorylation of the intracellular residues
= signalling inside the cell
54
how does IGF1R work
when IGF1 binds to extracellular alpha domain, induces a conformational change
tyrosine kinase within beta subunits becomes activated
autophosphorylation of the intracellular residues
= signalling inside the cell
55
intracellular signalling of IGF1-R
MAPK is coupled to mitogenesis
PKB pathway results in protection against apoptosis
= net effect of growth promotion
56
how does intracellular signalling of IGF1-R result sin growth promotion
MAPK is coupled to mitogenesis and PKB protects against apoptosis
57
what does MAPK do fro growth
coupled to mitogenesis
58
what does PKB do for growth
protects against apoptosis
59
what causes proportionate dwarfism
deficiency in GH
60
reduced cell growth can arise from
- decreased GH secretion
- defects in GH receptor
- defects in IGF-1 secretion
- defects in IGF-1 receptor
61
causes of decreased GH secretion
- GHRH receptor gene mutations
- anterior pituiatry failure
- GH gene mutations
62
what causes isolated GH deficiency
GHRH receptor gene mutations
63
how to treat decreased GH secretins
GH injections
64
what else is affected if GH is decreased from anterior pituiatry failure
TSH leading to metabolic defects
65
what causes defects in GH receptor
mutated GHR, GH resistance
66
example of GH receptor defects
Laron syndrome
67
laron syndrome
GH receptor defect
68
Plasma levels of GH and IGF1 in Laron syndrom
IGF-1 - low because GH cant stimulate secretio
| GH- high because no IGF-1 for negative feedback
69
treatment of defects in GH receptor
IGF-1 injections
70
what causes defects in IGF1 secretion
IGF-1 gene deletion
71
Plasma levels of GH and IGF1 when defects in IGF1 secretion
IGF1 levels undectable in plasma
| GH - high because no IGF-1 for negative feedback
72
treatment of defects in IGF-1 secretion
IGF-1 injections
73
what requires treatment of GH injections
decreased GH secretion
74
what requies treatment of IGF1 injections
impaired GH receptor, defects in IGF1 secretion
75
how to treat defects in IGF1 receptor
can't - its embryonically lethal becuase IGF1R plays key role in development of embryo
76
which growth defect is embryonically lethal
defects of the IGF1 receptor
77
when must treatments of GH or IGF1 problems be done
before end of puberty becuase that's when bones fuse
78
why must GH and IGF1 treatments be done before end of puberty
bones fuse
79
excess GH causes
gigantism
80
when is GH over secreted to cause gigantism
pre puberty
81
gigantism
over secretion of GH pre puberty
82
what does excess GH in childhood commonly cause
benign pituitary adenoma
83
what does excess GH in childhood raraely cause
gigantism
84
is gigantism proprtionate
yes; excess GH is pre puberty and so growth plates havent fused so there excessive height in proportionate with growth
85
treatment for gigantism
somatostatin analogues
86
treatment of most common effect of excess GH prepuberty
removal of benign pituitary adenoma
87
over secretion of GH post puberty causes
acromegaly
88
acromegaly
over secretion of GH post puberty
89
characteristics of acromegaly
thickiening of bones in the jaw, fingers and toes
90
why is acromegaly different to gigantism
growth plates have fused post-puberty, giving different effects in acromegaly
91
what does GH effect directly
metabolism
92
what does GH effect indirectly
growth
93
how does GH relate to inuslin
GH is counter-regualtory hormone that antagonises the effects of insulin
94
does GH antagonise or agonise the effects insulin
antagonise
95
when is GH present metabolically
fasting
96
effects of GH in fasting
- increases lipolysis
| - increases gluconeogenesis
97
what do the metabolic effects of GH prevent
they prevent hypoglycaemia when fuels are low by maintaining the balance of blood glucose
- lipolysis and gluconeogenesis
98
how does GH oppose the effects of insulin
Growth hormone makes muscle and adipose tissue less responsive to insulin ('insulin resistant') and so reduces glucose uptake by these tissues which reduces the storage of glucose during the absorptive phase and maintains high circulating levels of glucose. In this way growth hormone opposes the metabolic effects of insulin.
