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Endocrinology > Lec 11 - Human growth > Flashcards

Lec 11 - Human growth Flashcards

1
Q

when is max rate of growth

A

fetus
about 70cm/year

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2
Q

what cell behaviours are affected by growth hormone and IGF-1

A
  • survival (ie prevent or trigger apoptosis)
  • hypertrophy
  • proliferation
  • differentiation
  • metabolism
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3
Q

what does hypothal release

A

ghrh

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3
Q

what type of cell in the APG has the GHRH receptor

A

somatotrophs

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4
Q

what type of receptor is GHRH receptor

A

Gs GPCR
activates adenylyl cyclase = cAMP = activation of PKA

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5
Q

what tissues does GH directly act on

A
  • bone
  • adipose tissue
  • muscle
  • liver
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6
Q

where is igf1 produced

A

in liver mostly (can be in bone)
in response to GH stimulation

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7
Q

where does igf act

A
  • adipose tissue
    muscle
    etc.
    = endorcrine effects
  • but also bone
    = paracrine effects
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8
Q

GH gene

A

cluster of 5 closely related genes
GH-N = gh normal gene ie the one in circulation
(homology in between species as well)

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9
Q

whivh gh gene expressed in plactena

A

GH-V

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10
Q

GH-N codes for 2 different variations of GH, what are they

A

22kDa = the predominant one
20kDa (some residues deleted) = not sure what this one does

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11
Q

Gh produced as a precursor protein, what is cleaved when it gets secreted

A

n-terminal signal peptide

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12
Q

why would serial sampling be needed to take GH levels

A

secreted in pulses
and mostly at night

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13
Q

diff between struc of igf1 and gh

A

igf1 a much smaller peptide than gh

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14
Q

what are the 5 zones in bone

A
  • reserve zone
  • proliferative zone
  • maturation zone
  • hypertrophic zone
  • invasion zone
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15
Q

what does reserve zone contain

A

progenitor cells sat in matrix of collagen
provide cells that feed into next layers

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16
Q

what does proliferative zone contain

A

chondroblasts organised into columns

17
Q

what does maturation zone contain

A

the chondroblasts turn into chondrocytes
these secrete a matrix that forms scaffold for formation of trabecular bone

18
Q

what does hypertrophic zone

A

the cells grow in size duh
which then undergo apoptosis
which leave behind lacunae

19
Q

what does invasion zone contain

A

osteoblasts come up and deposit bone onto the scaffold left behind by chondrocytes

20
Q

which zones does gh and igf1 act on

A

all except invasion zone

21
Q

what 3 things does GH stimulate in terms of metabolsim

A
  • lipolysis
  • amino acid uptake and protein synth
  • glucose output from liver
22
Q

what 3 things does IGF1 stimulate in terms of metbaolism

A
  • lipogenesis
  • amino acid uptake and protein synth
  • uptake of glucose (similar to insulin)
23
Q

diff between gh and igf in terms of the receptors

A

gh receptor has to recruit an enzyme to the recpetor once bound

igf already has catalyitc activity built into the receptor

24
Q

fast and slow pathways in intracellular signalling

A

fast = kinase cascades
slow = e.g. GH stimulating production of igf1 by activating the gene

25
Q

what kind of receptor is GH receptor

A

homodimer

26
Q

what is 2 step model of GH biding

A
  • High affinity to first receptor
  • Then allows binding to lower affinity site on second receptor
    causes conformational change in receptor

= allows recruitment of JAK2 toreceptor
- JAK2 is a kinase = Phosphorylates the receptor
- Allows transc factor called stat5 to bind
- Then stat5 also becomes phosphorylated
- When stat 5 activated = binds to gene with response element (e.g. igf 1 gene)

27
Q

what is the GHBP

A

circulating GH is bound to binding protien
The binding protein is the extracellular portion of the protein
A protease cleaves this part off

27
Q

function of GHBP

A

Not much known about its significant
Ø May prolong GH half life
May compete GH receptor for GH

28
Q

what 2 cascades does IGF1 recpeotr trigger when igf binds

A
  • PI-3 kinase pathway
    = cell survival, metabolism
  • MAP kinase
    = proliferation
29
Q

how many igfbps are ther

A

6
all structually similar

30
Q

what is the main igfbp

A

igfbp 3

31
Q

function of igfbp 3

A

storage of IGF via ALS

32
Q

what is ALS

A

acid labile subunit
a very big complex that binds to IGFBP3
so it cant leave circulation
which keeps igf stored in circ

33
Q

how does IGFBP stop igf interacting with receptor

A

have a higher affinity than receptor to igf

34
Q

what 2 things negative ffedback on system

A

igf-1 = prevents GH from APG
and
somatostatin = prevents GHRH from hypothal

35
Q

what is Laron syndrome

A

mutated GH receptor

36
Q

what happens if hormone excess

A

depends if growth plate closed or not
if open = gigantism
if closed = acromegaly (abnormal growth)

37
Q

treatment of hormone excess

A

surgery
somatostatin analogue
GH receptor antagonist

38
Q
A

Endocrinology (25 decks)

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