MOLECULAR ENDOCRINOLOGY AND IMMUNOLOGY

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MOLECULAR ENDOCRINOLOGY AND IMMUNOLOGY LECTURE 7
- Mechanism of action of growth hormone and
prolactin
Growth hormone general actions receptor signal
transduction IGFs Prolactin actions on mammary
gland other actions receptor signal
transduction Mechanism of action of cytokines
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The GH-IGF-Somatic axis
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GH RECEPTOR

• First cloned (as cDNA) from rabbit and then
  human liver (Leung et al 1987)

Shown to be the real receptor by specificity,
and absence in patients with Laron dwarfism
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Cytokine receptors
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OVINE GH-RECEPTOR HOMOLOGY MODEL
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(No Transcript)
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GH-RECEPTOR INTERACTION
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JAK Kinases
Soluble tyrosine protein kinases, first named
just another kinase. Subsequently janus
kinases (because two apparent binding sites for
ATP) JAK1 JAK2 JAK3 Tyk
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GH Receptor and jak2
From Herrington Carter-Su (2001)
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GH signalling
From Herrington Carter-Su (2001)
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STAT signal transduction and activation of
transcription STAT1-STAT5 In 3T3-F442A cells
use of antisense knock-out of JAK2 or STAT5
eliminates GH actions. Depletion of MAPK pathway
and p70s6 kinase pathway does not
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Regulation of GH receptorJAK2 signaling
From Herrington Carter-Su (2001)
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The GH-IGF-Somatic axis
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THE SULPHATION FACTOR/SOMATOMEDIN/IGF
HYPOTHESIS Inject hypophysectomized rat with GH
induces growth and metabolism of cartilage
(including incorporation of 35SO4 into
cartilage) Incubate cartilage from hypox rat
with serum from hypox rat GH - no stimulation
of cartilage metabolism Incubate cartilage from
hypox rat with serum from GH-treated rat
-stimulation of cartilage metabolism SO GH
treatment leads to production of a factor in
serum which can stimulate cartilage metabolism
and growth
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Insulin-like growth factor I and II IGF I IGF
II Somatomedins Non-suppressible-insulin-like-ac
tivity (NSILA) Multiplication stimulating
activity (MSA)
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Sequence of IGF II
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Sequences of insulin and IGFs compared
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Precursors of insulin and IGFs
proinsulin
proIGF I
proIGF II
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3D structures of insulin and IGF
IGF II
Insulin
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The GH-IGF-Somatic axis
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Isaksson
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The GH-IGF-Somatic axis
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Endocrine control of mammary gland
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Mammary gland development
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Prolactin induces synthesis of the following
proteins Casein Alpha-lactalbumin Lactose
synthase Fatty acid synthetase
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Cytokine signalling
From Shillingford et al (2001)