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G0 G1

S

G2

M

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Control of Secretion

GHIH (or)

SST (somatostatin)

(-)

Anterior Pituitary:

Hypothalamus: GHRH

(+)

GH(somatotropin)

Liver: IGF (somatomedins)

(+)

(-)

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GROWTH HORMONE

direct effectsindirect effects

lipolysis in fat cells

+

carbohydrate

metabolism

+

Insulin-like Growth Factor

+

fat cells muscle

chondrocytes

Protein synthesis

cartilage formation

lipogenesis

Increases FFA, glycerol, and sugarsin circulation

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BrainPituitary

Liver

IGF

IGF binding proteins (IGFBPs)

Growth

Growth Hormone (GH)

GH/IGF/IGFBP Axis

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Insulin-like Growth Factor Binding Proteins(IGFBPs)

IGFBPs bind circulating IGF with highaffinity & specificity

Functions:1. act as carriers of IGF in plasma

2.

prolong the half-life of IGF in circulation3. regulate IGF access to receptor in

extracellular fluid (!)

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IGFBPstwo main types

1. IGFBP-3most abundant form of IGFBP

main carrier of IGF in circulation

promotes IGF mediated somatic growthhigh IGFBP-3 associated w/ growth stimulation

2. IGFBP-1typically present in small amountshigh IGFBP-1 associated w/ growth inhibition

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IGFBP-3

IGF

IGF receptor

LIVER

Cell

Growth Functions

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Cell

IGF receptor

LIVER

IGFBP-1

IGF

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Summary Growth factors move cell from G0to G1

Initiate cell cycle Growth Hormone

Direct effects: Lipolysis

Carbohydrate metabolism Increase IGF secretion from liver

Indirect effects through IGF Increase lipogenesis in fat cells Increase protein synthesis in muscle Increase cartilage formation and growth in bone

IGFBPs IGFBP3 enhances growth IGFBP1 inhibits growth

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Clinical Aspects

Stress effects on Growth

Overproduction of GH

Underproduction of GH End-organ resistance

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Maternal Effect: GC effect on Offspring

Japanese quail

From Hayward LS & Wingfield JC (2004) GCE 135:365-371Days after implantation

implants controls

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Human Studies

1. low birth weight

2. slow weight gain

3. smaller head size

4. are delayed in their walking

5. reduced speech development

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Direct Effect:

Stress-induced dwarfism

brought into the hospital months later

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BrainPituitary

Liver

IGF

IGF binding proteins (IGFBPs)

Growth

Growth Hormone (GH)

GH/IGF/IGFBP Axis

GCs

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Effects of Cortisol on Plasma IGF

Cortisol plasma IGF levels

Effect takes 24 hours FromKajimuraetal.(2003)

JOE178:91-99

control 2m

g/g 10m

g/g

Time (h)0 2 4 8 24PlasmaIGF(

ng/ml)

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Effects of Cortisol on Plasma IGFBPs

plasma IGFBP-3 levels

plasma IGFBP-1 levels

Cortisol induces rapidchanges in plasma IGFBPs

From

Kajimuraetal.(2003)

JOE178:91-99

Tilapia

control 2 mg/g 10 mg/g

IGFBP-3

O

DU

Time (h)

ODU

0 2 4 8 24

IGFBP-1

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Clinical Aspects

Stress Effects on Growth

GCs decrease growth

GCs can act through IGF or IGF binding

proteins Overproduction of GH

Underproduction of GH

End-organ resistance

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Acromegaly-overproduction of GH

-before puberty: gigantism (excessive growth of long bones)

-in adults: causes excessive growth of cartilage

-symptoms

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Clinical Aspects

Stress Effects on Growth

GCs decrease growth

GCs can act through IGF binding proteins

Overproduction of GHAcromegaly

gigantism

Underproduction of GH Hypo-pituitary dwarfism

End-organ resistance

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IGF levels

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Clinical Aspects

Overproduction of GH

Acromegaly

gigantism

Underproduction of GH

hypopituitary dwarfism

Stress-induced dwarfism

End-organ resistance

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Larons Syndrome

Defective GH receptor

recessive gene

Lethal in males

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Clinical Aspects

Overproduction of GH

Acromegaly

gigantism

Underproduction of GH

Hypopituitary dwarfism

Stress-induced dwarfism

End-organ resistance

Larons Syndrome

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bGH in Dairy Cows?

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Pygmies from Central Africa